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Haggstrom L, Chan WY, Nagrial A, Chantrill LA, Sim HW, Yip D, Chin V. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev 2024; 12:CD011044. [PMID: 39635901 PMCID: PMC11619003 DOI: 10.1002/14651858.cd011044.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
BACKGROUND Pancreatic cancer (PC) is a lethal disease with few effective treatment options. Many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review synthesises all the randomised data available to help better inform patient and clinician decision-making. It updates the previous version of the review, published in 2018. OBJECTIVES To assess the effects of chemotherapy, radiotherapy, or both on overall survival, severe or life-threatening adverse events, and quality of life in people undergoing first-line treatment of advanced pancreatic cancer. SEARCH METHODS We searched for published and unpublished studies in CENTRAL, MEDLINE, Embase, and CANCERLIT, and handsearched various sources for additional studies. The latest search dates were in March and July 2023. SELECTION CRITERIA We included randomised controlled trials comparing chemotherapy, radiotherapy, or both with another intervention or best supportive care. Participants were required to have locally advanced, unresectable pancreatic cancer or metastatic pancreatic cancer not amenable to curative intent treatment. Histological confirmation was required. Trials were required to report overall survival. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included 75 studies in the review and 51 in the meta-analysis (11,333 participants). We divided the studies into seven categories: any anti-cancer treatment versus best supportive care; various chemotherapy types versus gemcitabine; gemcitabine-based combinations versus gemcitabine alone; various chemotherapy combinations versus gemcitabine plus nab-paclitaxel; fluoropyrimidine-based studies; miscellaneous studies; and radiotherapy studies. In general, the included studies were at low risk for random sequence generation, detection bias, attrition bias, and reporting bias, at unclear risk for allocation concealment, and high risk for performance bias. Compared to best supportive care, chemotherapy likely results in little to no difference in overall survival (OS) (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.88 to 1.33; absolute risk of death at 12 months of 971 per 1000 versus 962 per 1000; 4 studies, 298 participants; moderate-certainty evidence). The adverse effects of chemotherapy and impacts on quality of life (QoL) were uncertain. Many of the chemotherapy regimens were outdated. Eight studies compared non-gemcitabine-based chemotherapy regimens to gemcitabine. These showed that 5-fluorouracil (5FU) likely reduces OS (HR 1.69, 95% CI 1.26 to 2.27; risk of death at 12 months of 914 per 1000 versus 767 per 1000; 1 study, 126 participants; moderate certainty), and grade 3/4 adverse events (QoL not reported). Fixed dose rate gemcitabine likely improves OS (HR 0.79, 95% CI 0.66 to 0.94; risk of death at 12 months of 683 per 1000 versus 767 per 1000; 2 studies, 644 participants; moderate certainty), and likely increase grade 3/4 adverse events (QoL not reported). FOLFIRINOX improves OS (HR 0.51, 95% CI 0.43 to 0.60; risk of death at 12 months of 524 per 1000 versus 767 per 1000; P < 0.001; 2 studies, 652 participants; high certainty), and delays deterioration in QoL, but increases grade 3/4 adverse events. Twenty-eight studies compared gemcitabine-based combinations to gemcitabine. Gemcitabine plus platinum may result in little to no difference in OS (HR 0.94, 95% CI 0.81 to 1.08; risk of death at 12 months of 745 per 1000 versus 767 per 1000; 6 studies, 1140 participants; low certainty), may increase grade 3/4 adverse events, and likely worsens QoL. Gemcitabine plus fluoropyrimidine improves OS (HR 0.88, 95% CI 0.81 to 0.95; risk of death at 12 months of 722 per 1000 versus 767 per 1000; 10 studies, 2718 participants; high certainty), likely increases grade 3/4 adverse events, and likely improves QoL. Gemcitabine plus topoisomerase inhibitors result in little to no difference in OS (HR 1.01, 95% CI 0.87 to 1.16; risk of death at 12 months of 770 per 1000 versus 767 per 1000; 3 studies, 839 participants; high certainty), likely increases grade 3/4 adverse events, and likely does not alter QoL. Gemcitabine plus taxane result in a large improvement in OS (HR 0.71, 95% CI 0.62 to 0.81; risk of death at 12 months of 644 per 1000 versus 767 per 1000; 2 studies, 986 participants; high certainty), and likely increases grade 3/4 adverse events and improves QoL. Nine studies compared chemotherapy combinations to gemcitabine plus nab-paclitaxel. Fluoropyrimidine-based combination regimens improve OS (HR 0.79, 95% CI 0.70 to 0.89; risk of death at 12 months of 542 per 1000 versus 628 per 1000; 6 studies, 1285 participants; high certainty). The treatment arms had distinct toxicity profiles, and there was little to no difference in QoL. Alternative schedules of gemcitabine plus nab-paclitaxel likely result in little to no difference in OS (HR 1.10, 95% CI 0.82 to 1.47; risk of death at 12 months of 663 per 1000 versus 628 per 1000; 2 studies, 367 participants; moderate certainty) or QoL, but may increase grade 3/4 adverse events. Four studies compared fluoropyrimidine-based combinations to fluoropyrimidines alone, with poor quality evidence. Fluoropyrimidine-based combinations are likely to result in little to no impact on OS (HR 0.84, 95% CI 0.61 to 1.15; risk of death at 12 months of 765 per 1000 versus 704 per 1000; P = 0.27; 4 studies, 491 participants; moderate certainty) versus fluoropyrimidines alone. The evidence suggests that there was little to no difference in grade 3/4 adverse events or QoL between the two groups. We included only one radiotherapy (iodine-125 brachytherapy) study with 165 participants. The evidence is very uncertain about the effect of radiotherapy on outcomes. AUTHORS' CONCLUSIONS Combination chemotherapy remains standard of care for metastatic pancreatic cancer. Both FOLFIRINOX and gemcitabine plus a taxane improve OS compared to gemcitabine alone. Furthermore, the evidence suggests that fluoropyrimidine-based combination chemotherapy regimens improve OS compared to gemcitabine plus nab-paclitaxel. The effects of radiotherapy were uncertain as only one low-quality trial was included. Selection of the most appropriate chemotherapy for individuals still remains unpersonalised, with clinicopathological stratification remaining elusive. Biomarker development is essential to assist in rationalising treatment selection for patients.
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Affiliation(s)
- Lucy Haggstrom
- Medical Oncology, The Kinghorn Cancer Care Centre, St Vincent's Hospital, Sydney, Australia
- Medical Oncology, Illawarra Shoalhaven Local Health District, Wollongong, Australia
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
| | - Wei Yen Chan
- Medical Oncology, The Kinghorn Cancer Care Centre, St Vincent's Hospital, Sydney, Australia
- Medical Oncology, Chris O'Brien Lifehouse, Sydney, Australia
| | - Adnan Nagrial
- The Crown Princess Mary Cancer Centre, Westmead, Australia
- Medical School, The University of Sydney, Sydney, Australia
| | - Lorraine A Chantrill
- Medical Oncology, Illawarra Shoalhaven Local Health District, Wollongong, Australia
- University of Wollongong, Wollongong, Australia
| | - Hao-Wen Sim
- Medical Oncology, The Kinghorn Cancer Care Centre, St Vincent's Hospital, Sydney, Australia
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Garran, Australia
- ANU Medical School, Australian National University, Acton, Australia
| | - Venessa Chin
- Medical Oncology, The Kinghorn Cancer Care Centre, St Vincent's Hospital, Sydney, Australia
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
- Medical Oncology, Garvan Institute of Medical Research, Sydney, Australia
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Tang CY, Yang SH, Li CP, Su YY, Chiu SC, Bai LY, Shan YS, Chen LT, Chuang SC, Chan DC, Yen CJ, Peng CM, Chiu TJ, Chen YY, Chen JS, Chiang NJ, Chou WC. Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer. Pancreatology 2024; 24:600-607. [PMID: 38565467 DOI: 10.1016/j.pan.2024.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 03/22/2024] [Accepted: 03/23/2024] [Indexed: 04/04/2024]
Abstract
BACKGROUND/OBJECTIVES Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.
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Affiliation(s)
- Cheng-Yu Tang
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chung-Pin Li
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yung-Yeh Su
- Department of Oncology, National Cheng Kung University Hospital, Taipei, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | | | - Li-Yuan Bai
- Division of Hematology-Oncology, Department of Internal Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
| | - Yan-Shen Shan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Chang Chuang
- Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - De-Chuan Chan
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, National Cheng Kung University Hospital, Taipei, Taiwan
| | - Cheng-Ming Peng
- Department of Surgery, Chung Shan Medical University Hospital and Chung Shan Medical University, Taichung, Taiwan
| | - Tai-Jan Chiu
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan
| | - Jen-Shi Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Nai-Jung Chiang
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Wen-Chi Chou
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Giordano G, Milella M, Landriscina M, Bergamo F, Tirino G, Santaniello A, Zaniboni A, Vasile E, De Vita F, Re GL, Vaccaro V, Giommoni E, Natale D, Conca R, Santini D, Maiorino L, Sanna G, Ricci V, Iop A, Montesarchio V, Procaccio L, Noventa S, Bianco R, Febbraro A, Lonardi S, Tortora G, Sperduti I, Melisi D. Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment. Cancer Med 2024; 13:e7345. [PMID: 38924262 PMCID: PMC11199338 DOI: 10.1002/cam4.7345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 05/11/2024] [Accepted: 05/18/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. METHODS The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. RESULTS AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. CONCLUSIONS This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.
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Affiliation(s)
- Guido Giordano
- Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical SciencesUniversity of FoggiaFoggiaItaly
| | - Michele Milella
- Section of Oncology, Department of MedicineUniversity of Verona School of Medicine and Verona University Hospital TrustVeronaItaly
| | - Matteo Landriscina
- Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical SciencesUniversity of FoggiaFoggiaItaly
| | | | - Giuseppe Tirino
- Unit of Medical Oncology, Sacro Cuore di Gesu'—Fatebenefratelli HospitalBeneventoItaly
| | - Antonio Santaniello
- Department of Clinical Medicine and SurgeryUniversity of Naples "Federico II"NaplesItaly
| | | | - Enrico Vasile
- Unit of Medical Oncology 2Azienda Ospedaliero‐Universitaria PisanaPisaItaly
| | - Ferdinando De Vita
- Division of Medical Oncology, Department of Precision MedicineUniversity of Campania "L. Vanvitelli"NaplesItaly
| | - Giovanni Lo Re
- Medical Oncology and Immune‐Related TumorsCentro di Riferimento Oncologico di Aviano (CRO), IRCCSAvianoItaly
| | - Vanja Vaccaro
- Medical Oncology 1IRCCS Regina Elena National Cancer InstituteRomeItaly
| | - Elisa Giommoni
- Medical Oncology UnitCareggi University HospitalFlorenceItaly
| | | | - Raffaele Conca
- Division of Medical Oncology, Department of Onco‐HematologyIRCCS‐CROB, Referral Cancer Center of BasilicataRionero in VultureItaly
| | - Daniele Santini
- Medical Oncology AUniversity of Rome, Policlinico Umberto I, "La SapienzaRomeItaly
| | | | - Gianni Sanna
- Medical OncologyIstituto Ospedaliero dell'Università di SassariSassariItaly
| | - Vincenzo Ricci
- Medical Oncology UnitAzienda Ospedaliera di Rilievo Nazionale ‘San Pio’BeneventoItaly
| | - Aldo Iop
- Department of OncologyAzienda Sanitaria Universitaria Giuliano Isontina (ASUGI)TriesteItaly
| | | | | | - Silvia Noventa
- Medical Oncology UnitFondazione PoliambulanzaBresciaItaly
| | - Roberto Bianco
- Department of Clinical Medicine and SurgeryUniversity of Naples "Federico II"NaplesItaly
| | - Antonio Febbraro
- Unit of Medical Oncology, Sacro Cuore di Gesu'—Fatebenefratelli HospitalBeneventoItaly
| | - Sara Lonardi
- Department of OncologyVeneto Institute of Oncology IRCCSPadovaItaly
| | - Giampaolo Tortora
- Oncologia MedicaFondazione Policlinico Universitario Gemelli IRCCSRomeItaly
- Oncologia MedicaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Isabella Sperduti
- Biostatistical UnitIRCCS Regina Elena National Cancer Institute, Istituti Fisioterapici OspitalieriRomeItaly
| | - Davide Melisi
- Section of Oncology, Department of MedicineUniversity of Verona School of Medicine and Verona University Hospital TrustVeronaItaly
- Investigational Cancer Therapeutics Clinical UnitAzienda Ospedaliera Universitaria IntegrataVeronaItaly
- Digestive Molecular Clinical Oncology Research UnitUniversity of VeronaVeronaItaly
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Fan M, Ma Y, Deng G, Si H, Jia R, Wang Z, Dai G. A real-world analysis of second-line treatment option, gemcitabine plus anlotinib and anti-PD1, in advanced pancreatic cancer. Pancreatology 2024; 24:579-583. [PMID: 38553260 DOI: 10.1016/j.pan.2024.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/04/2024] [Accepted: 03/23/2024] [Indexed: 06/12/2024]
Abstract
BACKGROUND In the second-line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nab-paclitaxel and Gemcitabine (Nab-P/Gem) or Nab-P combinations, second-line treatment were very limited. METHODS This is a retrospective single-center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second-line setting who have failed on the first-line Nab-P combinations. RESULTS In total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the second-line, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1-6.9) versus 3.5 months (95% CI 1.8-5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0-13.7) and 8.0 months (95% CI: 5.5-10.5) in FOLFORINOX group (p = 0.373). Grade ≥3 treatment-emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. CONCLUSION Our data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a well-tolerated regimen in the second-line treatment of APC and extends available data on its use as a second-line treatment option when compared with FOLFIRINOX.
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Affiliation(s)
- Mengjiao Fan
- Medical School of Chinese People's Liberation Army, Beijing, China; Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China; Medical Oncology Department, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Yue Ma
- Medical School of Chinese People's Liberation Army, Beijing, China; Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China; Medical Oncology Department, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Guochao Deng
- Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Haiyan Si
- Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Ru Jia
- Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Zhikuan Wang
- Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Guanghai Dai
- Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China; Medical Oncology Department, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
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Kodama T, Imajima T, Shimokawa M, Otsuka T, Kawahira M, Nakazawa J, Hori T, Shibuki T, Arima S, Ido A, Miwa K, Okabe Y, Koga F, Ueda Y, Kubotsu Y, Shimokawa H, Takeshita S, Nishikawa K, Komori A, Otsu S, Hosokawa A, Sakai T, Sakai K, Oda H, Kawahira M, Arita S, Honda T, Taguchi H, Tsuneyoshi K, Kawaguchi Y, Fujita T, Sakae T, Shirakawa T, Mizuta T, Mitsugi K. A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer. Sci Rep 2024; 14:12422. [PMID: 38816500 PMCID: PMC11139902 DOI: 10.1038/s41598-024-63172-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 05/27/2024] [Indexed: 06/01/2024] Open
Abstract
Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.
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Affiliation(s)
- Tomoko Kodama
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Takashi Imajima
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo-Shi, Nagasaki, 857-8575, Japan
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi‑ku, Fukuoka-Shi, Fukuoka, 812-8582, Japan
| | - Mototsugu Shimokawa
- Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka-Shi, Fukuoka, 811-1395, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube-Shi, Yamaguchi, 755-8505, Japan
| | - Taiga Otsuka
- Department of Internal Medicine, Minato Medical Clinic, 3-11-3 Nagahama, Chuo-Ku, Fukuoka-Shi, Fukuoka, 810-0072, Japan
| | - Masahiro Kawahira
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Junichi Nakazawa
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Takeshi Hori
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Taro Shibuki
- Department for the Promotion of Drug and Diagnostic Development, Division of Drug and Diagnostic Development Promotion, Translational Research Support Office, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-Shi, Chiba, 277-8577, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-Shi, Chiba, 277-8577, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima-Shi, Kagoshima, 890-8520, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima-Shi, Kagoshima, 890-8520, Japan
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
| | - Yoshinobu Okabe
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
| | - Futa Koga
- Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga-Shi, Saga, 840-8571, Japan
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine-Minami, Higashi-Ku, Kumamoto-Shi, Kumamoto, 861-8520, Japan
| | - Yoshihito Kubotsu
- Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada, Karatsu-Shi, Saga, 847-8588, Japan
| | - Hozumi Shimokawa
- Department of Hematology and Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-Ku, Kitakyushu-Shi, Fukuoka, 806-8501, Japan
| | - Shigeyuki Takeshita
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, 3-15 Morimachi, Nagasaki-Shi, Nagasaki, 852-8511, Japan
| | - Kazuo Nishikawa
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-Shi, Oita, 879-5593, Japan
| | - Azusa Komori
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-Shi, Oita, 879-5593, Japan
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-Machi, Matsuyama-Shi, Ehime, 791-0280, Japan
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-Shi, Oita, 879-5593, Japan
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, 5200 Kiyotakechoukihara, Miyazaki-Shi, Miyazaki, 889-1692, Japan
| | - Tatsunori Sakai
- Department of Medical Oncology, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-Ku, Kumamoto-Shi, Kumamoto, 860-0008, Japan
| | - Kenji Sakai
- Department of Medical Oncology, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-Ku, Kumamoto-Shi, Kumamoto, 860-0008, Japan
- Department of Clinical Oncology, Japan Community Health Care Organization Hitoyoshi Medical Center, 35 Oikamimachi, Hitoyoshi-Shi, Kumamoto, 868-8555, Japan
| | - Hisanobu Oda
- Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-Ku, Kumamoto-Shi, Kumamoto, 861-4193, Japan
| | - Machiko Kawahira
- Department of Gastroenterology, Kagoshima Kouseiren Hospital, 1-13-1 Yojirou, Kagoshima-Shi, Kagoshima, 890-0062, Japan
| | - Shuji Arita
- Department of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, 5-30 Kita-Takamatsucho, Miyazaki, 880-8510, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki-Shi, Nagasaki, 852-8501, Japan
| | - Hiroki Taguchi
- Department of Gastroenterology, Izumi General Medical Center, 520 Myoujin-Cho, Izumi-Shi, Kagoshima, 899-0131, Japan
- Department of Gastroenterology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Kengo Tsuneyoshi
- Department of Gastroenterology, Izumi General Medical Center, 520 Myoujin-Cho, Izumi-Shi, Kagoshima, 899-0131, Japan
| | - Yasunori Kawaguchi
- Department of Gastroenterology, Asakura Medical Association Hospital, 422-1 Raiha, Asakura-Shi, Fukuoka, 838-0069, Japan
| | - Toshihiro Fujita
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-Cho, Satsumasendai-Shi, Kagoshima, 895-0074, Japan
| | - Takahiro Sakae
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-Cho, Satsumasendai-Shi, Kagoshima, 895-0074, Japan
| | - Tsuyoshi Shirakawa
- Department of Medical Checkup Center, Eikoh Hospital, 3-8-15 Befu-Nishi, Shime-Machi, Kasuya-Gun, Fukuoka, 811-2232, Japan.
- Clinical Hematology Oncology Treatment Study Group, 1-14-6 Muromi-Gaoka, Nishi-Ku, Fukuoka-Shi, Fukuoka, 819-0030, Japan.
| | - Toshihiko Mizuta
- Department of Internal Medicine, Fujikawa Hospital, 1-2-6 Matsubara, Saga-Shi, Saga, 840-0831, Japan
| | - Kenji Mitsugi
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo-Shi, Nagasaki, 857-8575, Japan
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Hernández-Blanquisett A, Quintero-Carreño V, Martínez-Ávila MC, Porto M, Manzur-Barbur MC, Buendía E. Metastatic Pancreatic Cancer: Where Are We? Oncol Rev 2024; 17:11364. [PMID: 38304752 PMCID: PMC10830814 DOI: 10.3389/or.2023.11364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 12/20/2023] [Indexed: 02/03/2024] Open
Abstract
Pancreatic cancer is one of the most lethal neoplasms worldwide; it is aggressive in nature and has a poor prognosis. The overall survival rate for pancreatic cancer is low. Most patients present non-specific symptoms in the advanced stages, which generally leads to late diagnosis, at which point there is no option for curative surgery. The treatment of metastatic pancreatic cancer includes systemic therapy, in some cases radiotherapy, and more recently, molecular targeted therapies, which can positively impact cancer control and improve quality of life. This review provides an overview of the molecular landscape of pancreatic cancer based on the most recent literature, as well as current treatment options for patients with metastatic pancreatic cancer.
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Affiliation(s)
- Abraham Hernández-Blanquisett
- Cancer Institute, Hospital Serena del Mar, Cartagena, Colombia
- Clinical Oncology, Hospital Serena del Mar, Cartagena, Colombia
| | - Valeria Quintero-Carreño
- Cancer Institute, Hospital Serena del Mar, Cartagena, Colombia
- Pain and Palliative Care Department, Hospital Serena del Mar, Cartagena, Colombia
| | | | - María Porto
- Cancer Institute, Hospital Serena del Mar, Cartagena, Colombia
| | - María Carolina Manzur-Barbur
- Cancer Institute, Hospital Serena del Mar, Cartagena, Colombia
- Internal Medicine Department, Hospital Serena del Mar, Cartagena, Colombia
| | - Emiro Buendía
- Cancer Institute, Hospital Serena del Mar, Cartagena, Colombia
- Internal Medicine Department, Hospital Serena del Mar, Cartagena, Colombia
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8
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Pourali G, Donyadideh G, Mehrabadi S, Hamid F, Hassanian SM, Ferns GA, Khazaei M, Avan A. Clinical practice guidelines for interventional treatment of pancreatic cancer. RECENT ADVANCES IN NANOCARRIERS FOR PANCREATIC CANCER THERAPY 2024:345-373. [DOI: 10.1016/b978-0-443-19142-8.00008-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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9
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Wakabayashi M, Kikuchi Y, Yamaguchi K, Matsuda T. Prognosis of pancreatic cancer with Trousseau syndrome: a systematic review of case reports in Japanese literature. J Egypt Natl Canc Inst 2023; 35:40. [PMID: 38093170 DOI: 10.1186/s43046-023-00202-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
Trousseau syndrome is a paraneoplastic syndrome associated with a risk of poor prognosis. We reviewed the survival time and prognosis of patients with Trousseau syndrome. We identified 40 cases from 28 reports of Trousseau syndrome due to pancreatic cancer. We analyzed 20 cases based on reports providing sufficient information on the stage/location of pancreatic cancer and survival time after Trousseau syndrome. The median survival time was 2.0 months. There was no statistical difference between performance status (PS) 0-1 and PS 4, stages I-III and IV, and pancreatic head and body/tail. However, statistically significant differences were noted between the median survival time of patients who continued treatment for pancreatic cancer even after Trousseau syndrome and those who discontinued treatment (P = 0.005). Although only a small number of cases were analyzed in this study, the results indicated that patients with pancreatic cancer who developed Trousseau syndrome had a poor prognosis, and chemotherapy should be continued, if possible.
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Affiliation(s)
- Munehiro Wakabayashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Faculty of Medicine, School of Medicine, Toho University, Tokyo, Japan
| | - Yoshinori Kikuchi
- Department of Clinical Oncology, Faculty of Medicine, Toho University, Tokyo, 143-8541, Japan.
| | - Kazuhisa Yamaguchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Faculty of Medicine, School of Medicine, Toho University, Tokyo, Japan
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Faculty of Medicine, School of Medicine, Toho University, Tokyo, Japan
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10
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Fukahori M, Okabe Y, Shimokawa M, Otsuka T, Koga F, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Makiyama A, Taguchi H, Honda T, Ushijima T, Miwa K, Shibuki T, Nio K, Ide Y, Ureshino N, Mizuta T, Mitsugi K, Shirakawa T. Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer. Sci Rep 2023; 13:19399. [PMID: 37938630 PMCID: PMC10632451 DOI: 10.1038/s41598-023-46924-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 11/07/2023] [Indexed: 11/09/2023] Open
Abstract
First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27-0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58-1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.
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Affiliation(s)
- Masaru Fukahori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
- Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yoshinobu Okabe
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
| | - Mototsugu Shimokawa
- Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka-Shi, Fukuoka, 811-1395, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube-Shi, Yamaguchi, 755-8505, Japan
| | - Taiga Otsuka
- Department of Medical Oncology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga-Shi, Saga, 840-8571, Japan.
- Department of Internal Medicine, Minato Medical Clinic, 3-11-3 Nagahama, Chuo-Ku, Fukuoka-Shi, Fukuoka, 810-0072, Japan.
| | - Futa Koga
- Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga-Shi, Saga, 840-8571, Japan
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine-Minami, Higashi-Ku, Kumamoto-Shi, Kumamoto, 861-8520, Japan
| | - Junichi Nakazawa
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima-Shi, Kagoshima, 890-8760, Japan
| | - Azusa Komori
- Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-Machi, Yufu-Shi, Oita, 879-5593, Japan
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-Machi, Yufu-Shi, Oita, 879-5593, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima-Shi, Kagoshima, 890-8520, Japan
| | - Akitaka Makiyama
- Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-Ku, Kitakyushu-Shi, Fukuoka, 806-8501, Japan
- Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu-Shi, Gifu, 501-1194, Japan
| | - Hiroki Taguchi
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-Cho, Satsumasendai-Shi, Kagoshima, 895-0074, Japan
- Department of Gastroenterology, Imamura General Hospital, 11-23 Kamoike-Shinmachi, Kagoshima-Shi, Kagoshima, 890-0064, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki-Shi, Nagasaki, 852-8501, Japan
| | - Tomoyuki Ushijima
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-Machi, Kurume-Shi, Fukuoka, 830-0011, Japan
| | - Taro Shibuki
- Department of Internal Medicine, Imari Arita Kyoritsu Hospital, 860 Ninose-Ko, Arita-Cho, Nishi-Matsuura-Gun, Saga, 849-4193, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanohara, Kashiwa-Shi, Chiba, 277-8577, Japan
| | - Kenta Nio
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo-Shi, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-Ku, Fukuoka-Shi, Fukuoka, 810-8539, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada, Karatsu-Shi, Saga, 847-8588, Japan
| | - Norio Ureshino
- Department of Medical Oncology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga-Shi, Saga, 840-8571, Japan
- Department of Medical Oncology, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu-Shi, Chiba, 292-8535, Japan
| | - Toshihiko Mizuta
- Department of Internal Medicine, Imari Arita Kyoritsu Hospital, 860 Ninose-Ko, Arita-Cho, Nishi-Matsuura-Gun, Saga, 849-4193, Japan
- Department of Internal Medicine, Fujikawa Hospital, 1-2-6 Matsubara, Saga-Shi, Saga, 840-0831, Japan
| | - Kenji Mitsugi
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo-Shi, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-Ku, Fukuoka-Shi, Fukuoka, 810-8539, Japan
| | - Tsuyoshi Shirakawa
- Department of Medical Oncology, Fukuoka Wajiro Hospital, 2-2-75 Wajirogaoka, Higashi-Ku, Fukuoka-Shi, Fukuoka, 811-0213, Japan
- Department of Internal Medicine, Karatsu Higashi-Matsuura Medical Association Center, 2566-11 Chiyoda-machi, Karatsu-Shi, Saga, 847-0041, Japan
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Verbruggen L, Verheggen L, Vanhoutte G, Loly C, Lybaert W, Borbath I, Vergauwe P, Hendrickx K, Debeuckelaere C, de Haar-Holleman A, Van Laethem JL, Peeters M. A real-world analysis on the efficacy and tolerability of liposomal irinotecan plus 5-fluorouracil and folinic acid in metastatic pancreatic ductal adenocarcinoma in Belgium. Ther Adv Med Oncol 2023; 15:17588359231181500. [PMID: 37600936 PMCID: PMC10439761 DOI: 10.1177/17588359231181500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 05/24/2023] [Indexed: 08/22/2023] Open
Abstract
Background Currently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients. Objectives To provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk-benefit ratio of the intervention. Methods Medical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan-Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively. Results A total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/m² (range 49.24 mg/m²) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6-8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as later-line treatment was, respectively, 6.8 months (95% CI: 5.9-7.0 months) and 5.6 months (95% CI: 4.2-no upper limit). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4-4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8-4.8 months) while this was 2.4 months (95% CI: 1.9-9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4. Conclusion Nal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC. Trial details Retrospective study on the efficacy and tolerability of liposomal irinotecan (NALIRI); ClinicalTrials.gov Identifier: NCT0509506 (https://clinicaltrials.gov/ct2/show/NCT05095064?term=naliri&draw=2&rank=2).
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Affiliation(s)
- Lise Verbruggen
- Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital (UZA), Drie Eikenstraat 655, Edegem 2650, Belgium
| | - Lisa Verheggen
- Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Greetje Vanhoutte
- Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Catherine Loly
- Department of Gastroenterology, University Hospital CHU de Liège, Domaine Universitaire, Liège, Belgium
| | - Willem Lybaert
- Department of Medical Oncology, VITAZ, Sint-Niklaas, Belgium
| | - Ivan Borbath
- Department of Hepato-gastroenterology, Cliniques Universitaires Saint Luc, Brussels, Belgium
| | - Philippe Vergauwe
- Department of Gastroenterology, General Hospital Groeninge, Kortrijk, Belgium
| | - Koen Hendrickx
- Department of Gastroenterology, OLV Hospital, Aalst, Belgium
| | | | | | - Jean-Luc Van Laethem
- Department of Gastroenterology and Digestive Oncology, Erasme Hospital, Lenniks, Brussels, Belgium
| | - Marc Peeters
- Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital (UZA), Edegem, Belgium
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12
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Salazar J, Bracchiglione J, Savall-Esteve O, Antequera A, Bottaro-Parra D, Gutiérrez-Valencia M, Martínez-Peralta S, Pericay C, Tibau A, Bonfill X. Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review. BMC Cancer 2023; 23:748. [PMID: 37573294 PMCID: PMC10422698 DOI: 10.1186/s12885-023-11207-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/22/2023] [Indexed: 08/14/2023] Open
Abstract
BACKGROUND Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. METHODS We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. RESULTS We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. CONCLUSIONS The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.
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Affiliation(s)
- Josefina Salazar
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Javier Bracchiglione
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
- CIBER Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain
- Interdisciplinary Centre for Health Studies CIESAL, Universidad de Valparaíso, Viña del Mar, Chile
| | - Olga Savall-Esteve
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Alba Antequera
- International Health Department, ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
| | - David Bottaro-Parra
- Unitat de Cures Pal·Liatives de L'Institut d'Oncologia de La Catalunya Sud, Hospital Universitari Sant Joan de Reus, Tarragona, Spain
| | - Marta Gutiérrez-Valencia
- Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain
- Navarre Institute for Health Research (IdiSNA), Pamplona, Spain
| | | | - Carles Pericay
- Servicio de Oncología Médica, Fundació Assistencial Mûtua Terrassa, Terrassa - Barcelona, Spain
| | - Ariadna Tibau
- Oncology Department, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain
- Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain
- Universitat Autònoma Barcelona, Barcelona, Spain
| | - Xavier Bonfill
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
- CIBER Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain.
- Universitat Autònoma Barcelona, Barcelona, Spain.
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Takada R, Ikezawa K, Yamai T, Watsuji K, Seiki Y, Kawamoto Y, Hirao T, Higashi S, Urabe M, Kai Y, Nakabori T, Uehara H, Kotani M, Yagi T, Kimura M, Nozaki K, Takagi M, Ohkawa K. Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer. BMC Cancer 2023; 23:711. [PMID: 37518012 PMCID: PMC10388465 DOI: 10.1186/s12885-023-11205-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 07/21/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. METHODS We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. RESULTS The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. CONCLUSION The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.
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Affiliation(s)
- Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan.
| | - Takuo Yamai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Ko Watsuji
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Yusuke Seiki
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Yasuharu Kawamoto
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Takeru Hirao
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Sena Higashi
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Makiko Urabe
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Yugo Kai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Tasuku Nakabori
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Hiroyuki Uehara
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Michiyo Kotani
- Department of Nursing, Osaka International Cancer Institute, Osaka, Japan
| | - Toshinari Yagi
- Department of Outpatient Chemotherapy, Osaka International Cancer Institute, Osaka, Japan
| | - Miho Kimura
- Department of Pharmacy, Osaka International Cancer Institute, Osaka, Japan
| | - Keisuke Nozaki
- Department of Pharmacy, Osaka International Cancer Institute, Osaka, Japan
| | - Mari Takagi
- Department of Pharmacy, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
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14
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Komori A, Otsu S, Shimokawa M, Otsuka T, Koga F, Ueda Y, Nakazawa J, Arima S, Fukahori M, Okabe Y, Makiyama A, Taguchi H, Honda T, Shibuki T, Nio K, Ide Y, Ureshino N, Mizuta T, Shirakawa T, Mitsugi K. Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study. Int J Clin Oncol 2023:10.1007/s10147-023-02354-6. [PMID: 37209158 DOI: 10.1007/s10147-023-02354-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 05/05/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have few treatment options. It is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine + nab-PTX (GnP) or FOLFIRINOX. METHODS This analysis was conducted as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with metastatic pancreatic cancer. Excluding censored cases, 156 and 77 patients, respectively, received second-line chemotherapy (CTx) and best supportive care (BSC). Using prognostic factors for post-discontinuation survivals (PDSs) at the first-line determination in multivariate analysis, we developed a scoring system to demonstrate the benefit of second-line CTx. RESULTS The second-line CTx group had a median PDS of 5.2 months, whereas the BSC group had a median PDS of 2.7 months (hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01). According to the Cox regression model, serum albumin levels below 3.5 g/dL, and CA19-9 levels above 1000 U/mL were independent prognostic factors (p < 0.01). Serum albumin (≥ and < 3.5 g/dL allotted to scores 0 and 1) and CA19-9 (< and ≥ 1000 U/mL allotted to scores 0 and 1) at first-line determination were used to develop the scoring system. The PDSs of patients with scores of 0 and 1 were significantly better than those of the BSC group; however, there was no significant difference between the PDSs of patients with score 2 and the BSC group. CONCLUSION The survival advantage of second-line CTx, was observed in patients with scores of 0 and 1 but not in those with score 2.
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Affiliation(s)
- Azusa Komori
- Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-Machi, Matsuyama, Ehime, 791-0280, Japan
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Mototsugu Shimokawa
- Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka, Fukuoka, 811-1395, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Taiga Otsuka
- Department of Medical Oncology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga, Saga, 840-8571, Japan
- Department of Internal Medicine, Minato Medical Clinic, 3-11-3 Nagahama, Chuo-Ku, Fukuoka, Fukuoka, 810-0072, Japan
| | - Futa Koga
- Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga, Saga, 840-8571, Japan
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine-Minami, Higashi-Ku, Kumamoto, Kumamoto, 861-8520, Japan
| | - Junichi Nakazawa
- Department of Medical Oncology, Kagoshima City Hospital, 37-1 Uearata-Cho, Kagoshima, Kagoshima, 890-8760, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8520, Japan
| | - Masaru Fukahori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan
- Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yoshinobu Okabe
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan
| | - Akitaka Makiyama
- Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-Ku, Kitakyushu, Fukuoka, 806-8501, Japan
- Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Hiroki Taguchi
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-Cho, Satsumasendai, Kagoshima, 895-0074, Japan
- Department of Gastroenterology, Kagoshima City Hospital, 37-1 Uearata-cho, Kagoshima, Kagoshima, 890-8760, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan
| | - Taro Shibuki
- Department of Internal Medicine, Imari Arita Kyoritsu Hospital, 860 Ninose-Ko, Arita-Cho, Nishi-Matsuura-Gun, Saga, 849-4193, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Kenta Nio
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-Ku, Fukuoka, Fukuoka, 810-8539, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
- Department of Internal Medicine, National Hospital Organization Saga Hospital, 1-20-1 Hinode, Saga, Saga, 849-8577, Japan
| | - Norio Ureshino
- Department of Medical Oncology, Saga Medical Center Koseikan, 400 Kase-Machi, Saga, Saga, 840-8571, Japan
- Department of Medical Oncology, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu, Chiba, 292-8535, Japan
| | - Toshihiko Mizuta
- Department of Internal Medicine, Imari Arita Kyoritsu Hospital, 860 Ninose-Ko, Arita-Cho, Nishi-Matsuura-Gun, Saga, 849-4193, Japan
- Department of Internal Medicine, Fujikawa Hospital, 1-2-6 Matsubara, Saga, Saga, 840-0831, Japan
| | - Tsuyoshi Shirakawa
- Department of Medical Oncology, Fukuoka Wajiro Hospital, 2-2-75 Wajirogaoka, Higashi-Ku, Fukuoka, Fukuoka, 811-0213, Japan.
- Department of Internal Medicine, Karatsu Higashi-Matsuura Medical Association Center, 2566-11 Chiyoda-Machi, Karatsu, Saga, 847-0041, Japan.
| | - Kenji Mitsugi
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-Cho, Sasebo, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-Ku, Fukuoka, Fukuoka, 810-8539, Japan
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Słodkowski M, Wroński M, Karkocha D, Kraj L, Śmigielska K, Jachnis A. Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:cancers15092584. [PMID: 37174050 PMCID: PMC10177138 DOI: 10.3390/cancers15092584] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.
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Affiliation(s)
- Maciej Słodkowski
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
| | - Marek Wroński
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Dominika Karkocha
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Leszek Kraj
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Kaja Śmigielska
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Aneta Jachnis
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
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16
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Chaigneau T, Aguilera Munoz L, Oger C, Gourdeau C, Hentic O, Laurent L, Muller N, Dioguardi Burgio M, Gagaille MP, Lévy P, Rebours V, Hammel P, de Mestier L. Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens. Ther Adv Med Oncol 2023; 15:17588359231163776. [PMID: 37007630 PMCID: PMC10052496 DOI: 10.1177/17588359231163776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 02/24/2023] [Indexed: 03/30/2023] Open
Abstract
Background: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. Objectives: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. Design: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2–carboplatin between 2009 and 2021 in an expert center. Methods: We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. Results: In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2–carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0–6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4–3.0). At multivariable analysis, no extrahepatic metastases (p = 0.083), no ascites or opioid-requiring pain (p = 0.023), <2 prior treatment lines (p < 0.001), full dose of carboplatin (p = 0.004), and treatment initiation >18 months after initial diagnosis (p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48–4.92) and was influenced by the presence of extrahepatic metastases (p = 0.058), opioid-requiring pain or ascites (p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3–4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Conclusion: Although the efficacy of LV5FU2–carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.
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Affiliation(s)
- Thomas Chaigneau
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
- Department of Hepatology, Gastroenterology, and Nutrition, Caen-Normandie University Hospital, Caen, France
| | - Lina Aguilera Munoz
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Caroline Oger
- Université Paris-Cité, Department of Pharmacy and Chemotherapy, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Clémence Gourdeau
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
- Department of Hepatology and Gastroenterology, Rouen University Hospital, Rouen, France
| | - Olivia Hentic
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Lucie Laurent
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Nelly Muller
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Marco Dioguardi Burgio
- Université Paris-Cité, Department of Radiology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Marie-Pauline Gagaille
- Université Paris-Cité, Department of Pharmacy and Chemotherapy, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Philippe Lévy
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Vinciane Rebours
- Université Paris-Cité, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
| | - Pascal Hammel
- Université Paris-Cité, Department of Digestive and Medical Oncology, Beaujon Hospital (APHP.Nord), Clichy, France
- Université Paris-Saclay, Department of Digestive and Medical Oncology, Paul-Brousse Hospital (APHP.Sud), Villejuif, France
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17
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Beutel AK, Halbrook CJ. Barriers and opportunities for gemcitabine in pancreatic cancer therapy. Am J Physiol Cell Physiol 2023; 324:C540-C552. [PMID: 36571444 PMCID: PMC9925166 DOI: 10.1152/ajpcell.00331.2022] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 11/21/2022] [Accepted: 12/19/2022] [Indexed: 12/27/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDA) has become one of the leading causes of cancer-related deaths across the world. A lack of durable responses to standard-of-care chemotherapies renders its treatment particularly challenging and largely contributes to the devastating outcome. Gemcitabine, a pyrimidine antimetabolite, is a cornerstone in PDA treatment. Given the importance of gemcitabine in PDA therapy, extensive efforts are focusing on exploring mechanisms by which cancer cells evade gemcitabine cytotoxicity, but strategies to overcome them have not been translated into patient care. Here, we will introduce the standard treatment paradigm for patients with PDA, highlight mechanisms of gemcitabine action, elucidate gemcitabine resistance mechanisms, and discuss promising strategies to circumvent them.
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Affiliation(s)
- Alica K Beutel
- Department of Molecular Biology and Biochemistry, University of California, Irvine, California
- Department of Internal Medicine, University Hospital Ulm, Ulm, Germany
| | - Christopher J Halbrook
- Department of Molecular Biology and Biochemistry, University of California, Irvine, California
- Chao Family Comprehensive Cancer Center, Orange, California
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18
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Salazar J, Bracchiglione J, Acosta-Dighero R, Meza N, Meade AG, Quintana MJ, Requeijo C, Rodríguez-Grijalva G, Santero M, Selva A, Solà I, Bonfill X. Systemic oncological treatments in patients with advanced pancreatic cancer: a scoping review and evidence map. Support Care Cancer 2023; 31:100. [PMID: 36622453 PMCID: PMC9829581 DOI: 10.1007/s00520-022-07564-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/22/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE To identify, describe, and organise currently available evidence regarding systemic oncological treatments (SOTs) (chemotherapy, targeted/biological therapies, and immunotherapy) compared to best supportive care (BSC) for patients with advanced pancreatic cancer (PC). METHODS We conducted a scoping review and evidence mapping, adhering to PRISMA-ScR checklist. We searched MEDLINE, EMBASE, Cochrane Library, Epistemonikos, PROSPERO, and clinicaltrials.gov for eligible studies. We included systematic reviews (SRs), randomised controlled trials (RCTs), quasi-experimental, and observational studies evaluating SOTs compared to BSC or no treatment in patients with advanced PC. Two independent reviewers performed the screening process and data extraction. We developed evidence maps as an interactive visualization display, including the assessed interventions and outcomes. RESULTS Of the 50,601 records obtained from our search, we included 43 studies: 2 SRs, 16 RCTs, 4 quasi-experimental studies, 20 observational studies, and 1 protocol for a quasi-experimental study. Forty-two studies reported survival-related outcomes and most favoured SOTs, while five reported toxicity and most favoured BSC. Other patient-centred outcomes, such as quality of life, were scarcely reported. CONCLUSIONS This study highlights the current evidence gaps in studies assessing treatments for patients with advanced PC, mainly the lack of reports of non-survival-related outcomes, pointing out research areas that need further attention to make better recommendations for these patients.
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Affiliation(s)
- Josefina Salazar
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Javier Bracchiglione
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
- Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Viña del Mar, Chile
- CIBER Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain
| | - Roberto Acosta-Dighero
- Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Viña del Mar, Chile
| | - Nicolas Meza
- Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Viña del Mar, Chile
| | - Adriana-G Meade
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - María Jesús Quintana
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
- Universitat Autònoma Barcelona, Barcelona, Spain
| | - Carolina Requeijo
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | | | - Marilina Santero
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Anna Selva
- Universitat Autònoma Barcelona, Barcelona, Spain
- Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Ivan Solà
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
- CIBER Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain
- Universitat Autònoma Barcelona, Barcelona, Spain
| | - Xavier Bonfill
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
- CIBER Epidemiología Y Salud Pública (CIBERESP), Barcelona, Spain.
- Universitat Autònoma Barcelona, Barcelona, Spain.
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19
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Saoudi González N, Castet F, Élez E, Macarulla T, Tabernero J. Current and emerging anti-angiogenic therapies in gastrointestinal and hepatobiliary cancers. Front Oncol 2022; 12:1021772. [PMID: 36300092 PMCID: PMC9589420 DOI: 10.3389/fonc.2022.1021772] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 09/26/2022] [Indexed: 09/07/2024] Open
Abstract
Gastrointestinal tumours are a heterogeneous group of neoplasms that arise in the gastrointestinal tract and hepatobiliary system. Their incidence is rising globally and they currently represent the leading cause of cancer-related mortality worldwide. Anti-angiogenic agents have been incorporated into the treatment armamentarium of most of these malignancies and have improved survival outcomes, most notably in colorectal cancer and hepatocellular carcinoma. New treatment combinations with immunotherapies and other agents have led to unprecedented benefits and are revolutionising patient care. In this review, we detail the mechanisms of action of anti-angiogenic agents and the preclinical rationale underlying their combinations with immunotherapies. We review the clinical evidence supporting their use across all gastrointestinal tumours, with a particular emphasis on colorectal cancer and hepatocellular carcinoma. We discuss available biomarkers of response to these therapies and their utility in routine clinical practice. Finally, we summarise ongoing clinical trials in distinct settings and highlight the preclinical rationale supporting novel combinations.
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Affiliation(s)
| | | | | | - Teresa Macarulla
- Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
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21
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Miki M, Lee L, Hisano T, Sugimoto R, Furukawa M. Loss of adipose tissue or skeletal muscle during first-line gemcitabine/nab-paclitaxel therapy is associated with worse survival after second-line therapy of advanced pancreatic cancer. Asia Pac J Clin Oncol 2022; 18:e297-e305. [PMID: 34818466 PMCID: PMC9541259 DOI: 10.1111/ajco.13669] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/17/2021] [Indexed: 12/18/2022]
Abstract
AIM Progression of cachexia indicated by decreased body weight and composition is associated with poor survival of advanced pancreatic cancer (APC). There are limited data concerning the prognostic effect of cachexia on second-line chemotherapy (L2). We aimed to assess the impact of cachexia progression during first-line therapy (L1) on survival after L2. METHODS We reviewed patients with gemcitabine/nab-paclitaxel (GEM/nabPTX)-refractory APC who underwent L2 with modified FOLFIRINOX or S-1 between 2015 and 2019 in our institution. We determined clinicopathological data including body composition parameters: subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle index (SMI). Correlations of changes in these parameters, as well as their effect on overall survival after L2 (OS2), were examined. RESULTS Median rates of change in SMI, SFA, and VFA were 0.19%, -4.17%, and -18.39%, respectively, in 59 patients during L1. Although there was moderate correlation in rate of change between SFA and VFA, there was no correlation between SMI and other parameters. We defined loss of SFA, VFA, and SMI as decreases greater than 8.5%, 34.1%, and 8.7%, respectively. Median OS2 of patients with loss in any of these parameters was significantly shorter than in patients without loss (3.83 vs. 8.73 months). Multivariate analysis revealed that loss in any parameters, performance status, and C-reactive protein/albumin ratio were independent negative prognostic factors. CONCLUSION Loss of adipose tissue or skeletal muscle during L1 had a considerable impact on OS2 in APC refractory to GEM/nabPTX.
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Affiliation(s)
- Masami Miki
- Department of Hepato‐Biliary‐PancreatologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Lingaku Lee
- Department of Hepato‐Biliary‐PancreatologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Terumasa Hisano
- Department of Hepato‐Biliary‐PancreatologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Rie Sugimoto
- Department of Hepato‐Biliary‐PancreatologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Masayuki Furukawa
- Department of Hepato‐Biliary‐PancreatologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
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22
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Liu T, Cheng S, Xu Q, Wang Z. Management of Advanced Pancreatic Cancer through Stromal Depletion and Immune Modulation. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58091298. [PMID: 36143975 PMCID: PMC9502806 DOI: 10.3390/medicina58091298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 11/16/2022]
Abstract
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Unfortunately, therapeutic gains in the treatment of other cancers have not successfully translated to pancreatic cancer treatments. Management of pancreatic cancer is difficult due to the lack of effective therapies and the rapid development of drug resistance. The cytotoxic agent gemcitabine has historically been the first-line treatment, but combinations of other immunomodulating and stroma-depleting drugs are currently undergoing clinical testing. Moreover, the treatment of pancreatic cancer is complicated by its heterogeneity: analysis of genomic alterations and expression patterns has led to the definition of multiple subtypes, but their usefulness in the clinical setting is limited by inter-tumoral and inter-personal variability. In addition, various cell types in the tumor microenvironment exert immunosuppressive effects that worsen prognosis. In this review, we discuss current perceptions of molecular features and the tumor microenvironment in pancreatic cancer, and we summarize emerging drug options that can complement traditional chemotherapies.
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Affiliation(s)
- Tiantong Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100006, China
| | - Sihang Cheng
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100006, China
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100006, China
- Correspondence: (Q.X.); (Z.W.); Tel.: +86-10-69156007 (Q.X.); +86-10-69159567 (Z.W.)
| | - Zhiwei Wang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100006, China
- Correspondence: (Q.X.); (Z.W.); Tel.: +86-10-69156007 (Q.X.); +86-10-69159567 (Z.W.)
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23
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Striefler JK, Stieler JM, Neumann CCM, Geisel D, Ghadjar P, Sinn M, Malinka T, Pratschke J, Stintzing S, Oettle H, Riess H, Pelzer U. Dual Targeting of the EGFR/HER2 Pathway in Combination with Systemic Chemotherapy in Refractory Pancreatic Cancer-The CONKO-008 Phase I Investigation. J Clin Med 2022; 11:jcm11164905. [PMID: 36013144 PMCID: PMC9409879 DOI: 10.3390/jcm11164905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/11/2022] [Accepted: 08/17/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. Methods: We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m2 day + 5-fluorouracil 2000 mg/m2 (24 h) on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 days 8 and 22 of a 43-day cycle (OFF). Toxicity and efficacy were evaluated. Results: In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. Conclusions: The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.
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Affiliation(s)
- Jana K. Striefler
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
| | | | - Christopher C. M. Neumann
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
| | - Dominik Geisel
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
| | - Pirus Ghadjar
- Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Thomas Malinka
- Department of Surgery, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
| | - Sebastian Stintzing
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
| | - Helmut Oettle
- Outpatient Department, 88045 Friedrichshafen, Germany
| | - Hanno Riess
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- Correspondence: ; Tel.: +49-30450513556
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Iede K, Yamada T, Ueda M, Tsuda Y, Nakashima S, Ohta K, Tanida T, Matsuyama J, Ikenaga M, Tominaga S. Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer. Medicine (Baltimore) 2022; 101:e29532. [PMID: 35866833 PMCID: PMC9302340 DOI: 10.1097/md.0000000000029532] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.
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Affiliation(s)
- Kiyotsugu Iede
- Departments of Clinical Oncology and Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Terumasa Yamada
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
- *Correspondence: Terumasa Yamada, Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka 578-8588, Japan (e-mail: )
| | - Masami Ueda
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Yujiro Tsuda
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Shinsuke Nakashima
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Katsuya Ohta
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Tsukasa Tanida
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Jin Matsuyama
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Masakazu Ikenaga
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Shusei Tominaga
- Departments of Clinical Oncology and Higashiosaka City Medical Center, Higashiosaka, Japan
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Zaibet S, Hautefeuille V, Auclin E, Lièvre A, Tougeron D, Sarabi M, Gilabert M, Wasselin J, Edeline J, Artru P, Bechade D, Morin C, Ducoulombier A, Taieb J, Pernot S. Gemcitabine + Nab-paclitaxel or Gemcitabine alone after FOLFIRINOX failure in patients with metastatic pancreatic adenocarcinoma: a real-world AGEO study. Br J Cancer 2022; 126:1394-1400. [PMID: 35094032 PMCID: PMC9091233 DOI: 10.1038/s41416-022-01713-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 12/20/2021] [Accepted: 01/20/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Gemcitabine (Gem) alone or with Nab-paclitaxel (Gem-Nab) is used as second-line treatment for metastatic pancreatic adenocarcinoma (mPA) after FOLFIRINOX (FFX) failure; however, no comparative data exist. This study evaluates the efficacy and safety of adding Nab-paclitaxel to Gem for mPA after FFX failure. METHODS In this retrospective real-world multicenter study, from 2011 to 2019, patients with mPA receiving Gem-Nab (Gem 1000 mg/m² + Nab 125 mg/m², 3 out of 4 weeks) or Gem alone were included after progression on FFX. RESULTS A total of 427 patients were included. Patients receiving Gem-Nab had more metastatic sites, peritoneal disease and less PS 2 (24% vs. 35%). After median follow-up of 22 months, Gem-Nab was associated with better disease control rate (DCR) (56% vs. 32%; P < 0.001), progression-free survival (PFS) (3.5 vs. 2.3 months; 95% CI: 0.43-0.65) and overall survival (OS) (7.1 vs. 4.7 months; 95% CI: 0.53-0.86). After multivariate analysis, Gem-Nab and PS 0/1 were associated with better OS and PFS. Grade 3/4 toxicity was more frequent with Gem-Nab (44% vs. 29%). CONCLUSION In this study, Gem-Nab was associated with better DCR, PFS and OS compared with Gem alone in patients with mPA after FFX failure, at the cost of higher toxicity.
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Affiliation(s)
- Sonia Zaibet
- Department of Hepato-Gastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges Pompidou, Université de Paris, SIRIC CARPEM Comprehensive Cancer Center, Paris, France
| | - Vincent Hautefeuille
- Department of Hepato-Gastroenterology and Gastrointestinal Oncology, CHU Amiens Picardie, Amiens, France
| | - Edouard Auclin
- Department of Medical Oncology, Hôpital Européen Georges Pompidou, Université de Paris, SIRIC CARPEM Comprehensive Cancer Center, Paris, France
- INSERM, UMR 1138, team 22, Centre de Recherche des Cordeliers, Université de Paris, Paris, France
| | - Astrid Lièvre
- Department of Gastroenterology, CHU Rennes, INSERM U1242, Rennes, France
| | - David Tougeron
- Department of Hepato-Gastroenterology, CHU Poitiers, Poitiers, France
| | - Mathieu Sarabi
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
| | - Marine Gilabert
- Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
| | - Julie Wasselin
- Department of Hepato-Gastroenterology and Gastrointestinal Oncology, CHU Amiens Picardie, Amiens, France
| | - Julien Edeline
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Pascal Artru
- Department of Hepato-Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France
| | | | - Clémence Morin
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
| | | | - Julien Taieb
- Department of Hepato-Gastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges Pompidou, Université de Paris, SIRIC CARPEM Comprehensive Cancer Center, Paris, France
| | - Simon Pernot
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
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Helical tomotherapy for asymptomatic chemotherapy-refractory or -unfit multiple (3 or more) metastases. Rep Pract Oncol Radiother 2022; 27:125-133. [PMID: 35402042 PMCID: PMC8989439 DOI: 10.5603/rpor.a2022.0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 01/16/2022] [Indexed: 11/26/2022] Open
Abstract
Background Despite chemotherapy innovations, prognosis of patients with chemotherapy-refractory or -unfit multiple metastases (CRMM/CUMM) remains poor. In this prospective study, the efficacy and toxicity of helical tomotherapy for CRMM/CUMM were evaluated. Materials and methods Between 2014 and 2020, asymptomatic patients with CRMM/CUMM with ≥ 3 lesions and no prior radiotherapy of the targets were enrolled. Patients who had intolerable toxicities to chemotherapy and those who refused chemotherapy were included in the CRMM and CUMM groups, respectively. Prostate cancer patients and patients with metastases mainly localized in the liver, lung, or brain were excluded. By helical tomotherapy, up to 10 lesions per patient were irradiated in order of volume. The standard dose was 50–60 Gy in 25–30 fractions. Results Forty-five patients (median age, 63 years; 35 CRMM/10 CUMM) were enrolled. Primary tumors included lung, gynecological, and gastrointestinal cancers. The most frequently treated targets were lymph node metastases, followed by peritoneal/pleural disseminations and bone tumors. The 1-year survival rate was 51% (median, 12.5 months). In the 35 patients with CRMM, the median survival time was 12.5 months, and the median pre-radiation chemotherapy period was 8.8 months (p > 0.05). The 6-month target control rate was 78%. Acute adverse events (grade ≥ 2) occurred in 33 patients: hematologic toxicities in 23, dermatitis in 6, and others in 8. Late grade ≥ 2 toxicities occurred in 6 patients: pneumonitis in 4 and gastric hemorrhage in 2. Conclusion Tomotherapy for CRMM/CUMM resulted in median survival times > 1 year. This treatment should be investigated further in larger prospective studies.
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Yamai T, Ikezawa K, Kawamoto Y, Hirao T, Higashi S, Daiku K, Maeda S, Abe Y, Urabe M, Kai Y, Takada R, Nakabori T, Uehara H, Ohkawa K. 5-Fluorouracil/L-Leucovorin Plus Oxaliplatin (FOLFOX) Regimen as Salvage Chemotherapy for Patients with Unresectable Pancreatic Cancer Receiving Gemcitabine and Nab-Paclitaxel and 5-Fluorouracil/L-Leucovorin Plus Nanoliposomal Irinotecan: Preliminary Results from Clinical Practice. Curr Oncol 2022; 29:2644-2649. [PMID: 35448190 PMCID: PMC9026505 DOI: 10.3390/curroncol29040216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/30/2022] [Accepted: 04/08/2022] [Indexed: 12/24/2022] Open
Abstract
Salvage chemotherapy for patients with unresectable pancreatic cancer (UR-PC) who have been treated with gemcitabine and nab-paclitaxel (GnP), and 5-fluorouracil (5-FU)/l-leucovorin (LV) plus nanoliposomal irinotecan (nal-IRI), has not been fully established. We retrospectively reviewed data from 17 patients with UR-PC who initiated 5-FU/l-LV plus oxaliplatin (FOLFOX) as salvage chemotherapy at our hospital between June 2020 and August 2021, after treatment with GnP and 5-FU/LV plus nal-IRI. The primary endpoint was tumor response. The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). The response and disease control rates were 5.9% (1/17) and 17.6% (3/17), respectively. The median PFS was 1.8 months (range: 0.4-5.2 months). Eight patients (47.1%) experienced grade 3 nonhematologic AEs, while none experienced grade 3 hematologic AEs. Two patients with controlled disease had homologous recombination deficiency (HRD)-associated gene mutations in cancer panel testing. The FOLFOX regimen benefit for UR-PC patients treated with GnP and 5-FU/LV plus nal-IRI may be limited to patients with HRD-associated gene mutations.
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Affiliation(s)
| | - Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chou-ku, Osaka 541-8567, Japan; (T.Y.); (Y.K.); (T.H.); (S.H.); (K.D.); (S.M.); (Y.A.); (M.U.); (Y.K.); (R.T.); (T.N.); (H.U.); (K.O.)
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Iede K, Yamada T, Koh M, Ueda M, Tsuda Y, Nakashima S, Ohta K, Tanida T, Matsuyama J, Ikenaga M, Tominaga S. Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer. Pancreas 2022; 51:278-281. [PMID: 35584386 DOI: 10.1097/mpa.0000000000002013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.
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Affiliation(s)
| | - Terumasa Yamada
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Masahiro Koh
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Masami Ueda
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Yujiro Tsuda
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Shinsuke Nakashima
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Katsuya Ohta
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Tsukasa Tanida
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Jin Matsuyama
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
| | - Masakazu Ikenaga
- Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan
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Lundy J, Harris M, Zalcberg J, Zimet A, Goldstein D, Gebski V, Borsaru A, Desmond C, Swan M, Jenkins BJ, Croagh D. EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy. Front Oncol 2021; 11:770022. [PMID: 34956889 PMCID: PMC8696205 DOI: 10.3389/fonc.2021.770022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 11/18/2021] [Indexed: 12/27/2022] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach. Patients and Methods Fresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS). Results 275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia. Conclusions This study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population.
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Affiliation(s)
- Joanne Lundy
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia.,Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia
| | - Marion Harris
- Department of Oncology, Faculty of Medicine, Nursing and Health Sciences and School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - John Zalcberg
- Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia.,Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Allan Zimet
- Department of Medical Oncology, Epworth Hospital, Melbourne, VIC, Australia
| | - David Goldstein
- Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.,Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW, Australia
| | - Val Gebski
- National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia
| | - Adina Borsaru
- Diagnostic Imaging, Monash Health, Melbourne, VIC, Australia
| | | | - Michael Swan
- Department of Gastroenterology, Monash Health, Melbourne, VIC, Australia
| | - Brendan J Jenkins
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia
| | - Daniel Croagh
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia.,Department of Surgery, Epworth Healthcare, Melbourne, VIC, Australia
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30
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Cleary JM, Wolpin BM, Dougan SK, Raghavan S, Singh H, Huffman B, Sethi NS, Nowak JA, Shapiro GI, Aguirre AJ, D'Andrea AD. Opportunities for Utilization of DNA Repair Inhibitors in Homologous Recombination Repair-Deficient and Proficient Pancreatic Adenocarcinoma. Clin Cancer Res 2021; 27:6622-6637. [PMID: 34285063 PMCID: PMC8678153 DOI: 10.1158/1078-0432.ccr-21-1367] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/04/2021] [Accepted: 07/06/2021] [Indexed: 11/16/2022]
Abstract
Pancreatic cancer is rapidly progressive and notoriously difficult to treat with cytotoxic chemotherapy and targeted agents. Recent demonstration of the efficacy of maintenance PARP inhibition in germline BRCA mutated pancreatic cancer has raised hopes that increased understanding of the DNA damage response pathway will lead to new therapies in both homologous recombination (HR) repair-deficient and proficient pancreatic cancer. Here, we review the potential mechanisms of exploiting HR deficiency, replicative stress, and DNA damage-mediated immune activation through targeted inhibition of DNA repair regulatory proteins.
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Affiliation(s)
- James M Cleary
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
| | - Brian M Wolpin
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Stephanie K Dougan
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Srivatsan Raghavan
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Harshabad Singh
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Brandon Huffman
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Nilay S Sethi
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Jonathan A Nowak
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Geoffrey I Shapiro
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
- Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Andrew J Aguirre
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Alan D D'Andrea
- Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
- Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Boston, Massachusetts
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31
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Ekström A, Brun E, Eberhard J, Segerlantz M. Second-line palliative chemotherapy, survival, and prognostic factors in patients with advanced pancreatic cancer. Acta Oncol 2021; 60:1580-1588. [PMID: 34486921 DOI: 10.1080/0284186x.2021.1973680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Pancreatic cancer is a highly lethal disease with a close association between incidence and mortality. First-line (FL) palliative chemotherapy prolongs survival and alleviates cancer-related symptoms. However, the survival benefit of second-line (SL) treatment is uncertain, as studies fail to consistently show prolonged survival for any given SL treatment, and in the absence of prognostic factors patients will receive a futile treatment. The aim of this study was to examine prognostic factors and survival in patients with pancreatic cancer, with special reference to SL therapy. MATERIAL AND METHODS This retrospective study included all patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between 1 Feb 2015 and 31 Dec 2017. RESULTS During the study period, a total of 170 patients with pancreatic cancer died after receiving palliative chemotherapy. Of these, 72 had received SL treatment after progression on FL treatment. Median overall survival (OS) from the start of SL treatment was 5.0 months (95% CI: 4.0-6.1). Median OS was 2.9 months for patients with performance status 2 at start of SL treatment compared to 5.3 months for patients with performance status 0-1 (p = .03), and 3.5 months (95% CI: 3.0-5.4) in patients with hypoalbuminemia (<36 g/L) at the start of SL therapy compared to 8.0 months (95% CI: 5.3-11.1) for patients with normal albumin levels (p = .009). Weight loss during FL therapy, a doubling of CA 19-9 after FL therapy, and length of progression-free survival during FL treatment were not associated with survival following SL therapy. CONCLUSION Poor performance status and hypoalbuminemia are negative prognostic factors for survival on SL palliative treatment in patients with advanced pancreatic cancer. Possible gain in survival should be carefully considered before initiating SL chemotherapy.
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Affiliation(s)
- Anders Ekström
- Department of Clinical Sciences, Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Oncology, Blekinge Hospital, Karlskrona, Sweden
| | - Eva Brun
- Department of Clinical Sciences, Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Oncology, Skåne University Hospital, Lund, Sweden
| | - Jakob Eberhard
- Department of Clinical Sciences, Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Oncology, Skåne University Hospital, Lund, Sweden
| | - Mikael Segerlantz
- Department of Clinical Sciences Lund, Oncology and Pathology, Institute for Palliative Care, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Palliative Care and Advanced Home Health Care, Primary Health Care Skåne, Region Skåne, Lund, Sweden
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Chiu TJ, Su YY, Yang SH, Li CP, Bai LY, Chiang NJ, Chuang SC, Shan YS, Chan DC, Chen LT, Yen CJ, Peng CM, Chen YY, Chen JS, Chou WC. Liposomal irinotecan pre-emptive dose reduction in patients with pancreatic ductal adenocarcinoma: 667 patients' experience within a population-based study. Ther Adv Med Oncol 2021; 13:17588359211058255. [PMID: 34819998 PMCID: PMC8606735 DOI: 10.1177/17588359211058255] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/20/2021] [Indexed: 12/27/2022] Open
Abstract
Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC. Methods: We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50–74%, <50%) for comparison of treatment efficacy and safety. Results: The median overall survival (OS) and time to treatment failure (TTF) were 5.9 months [95% confidence interval (CI), 5.3–6.5] and 2.8 months (95% CI, 2.6–3.0), respectively. The median OS was 6.5 months (95% CI, 5.7–6.7), 5.0 months (95% CI, 3.4–6.5), and 4.1 months (95% CI, 2.7–5.6), respectively, among the ⩾75%, 50–74%, and <50% pre-emptive nal-IRI dosing groups, whereas the median TTF of the three groups was 3.0 months (95% CI, 2.6–3.4), 2.6 months (95% CI, 2.3–2.9), and 1.9 months (95% CI, 1.6–2.2), respectively. Pre-emptive nal-IRI dosing <50% was an independent negative prognostic factor for OS and TTF in multivariate analyses. The most common severe adverse events were neutropenia (22.9%), anemia (21.1%), and hypokalemia (15.4%). Patients in the <50% pre-emptive nal-IRI dosing group had a significantly lower incidence of neutropenia and non-neutropenic infection than those in the other groups. Conclusion: Our results support the use of nal-IRI + 5-FU/LV as standard clinical practice for treating patients with PDAC based on this large population-based study. Our findings encourage physicians to provide adequate doses of nal-IRI in order to achieve better outcomes without compromising safety profiles.
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Affiliation(s)
- Tai-Jan Chiu
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung
| | - Yung-Yeh Su
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital, National Taiwan University, Taipei
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine and Division of Clinical Skills Training, Taipei
| | - Li-Yuan Bai
- Division of Hematology-Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung
| | - Nai-Jung Chiang
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Shih-Chang Chuang
- Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Yan-Shen Shan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan
| | - De-Chuan Chan
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Chia-Jui Yen
- Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Cheng-Ming Peng
- Department of Surgery, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung
| | - Jen-Shi Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan
| | - Wen-Chi Chou
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 5 Fu-Hsing Street, 333 Kwei-Shan Shiang, Taoyuan
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Rogers JE, Mizrahi JD, Nogueras Gonzalez GM, Surana R, Shroff RT, Wolff R, Varadhachary GR, Javle MM, Overman M, Raghav K, Pant S. Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging. J Gastrointest Oncol 2021; 12:2268-2274. [PMID: 34790391 DOI: 10.21037/jgo-20-569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 06/08/2021] [Indexed: 11/06/2022] Open
Abstract
Background Objective responses to first-line systemic chemotherapy in metastatic pancreatic cancer patients are seen in less than one third of cases. Unfortunately, a significant amount will have disease progression (PD) on their first restaging imaging. With patients' short life expectancy, it is crucial for clinicians to be prudent when deciding whom and when to treat. Our study aimed to evaluate outcomes of patients that progressed on their first restaging imaging on 1st line therapy. Methods We retrospectively analyzed patients diagnosed between 2010-2017 whose first restaging imaging demonstrated PD. The primary outcome was overall survival (OS) from metastatic diagnosis date to death. Patients who were lost to follow-up were excluded. Results Out of 262 total patients reviewed, 98 patients (37%) were included. Sixty-five (66%) received 2nd line therapy, and 33 (34%) did not. Reasons patients did not pursue 2nd line therapy were performance status (PS) decline, organ dysfunction, or patient choice for alternative therapy. Median ages for patients who did and did not receive 2nd line therapy were 61 and 67, respectively (P<0.001). More patients had a poor PS at the time of initial diagnosis in the non-2nd line therapy group (7.5% vs. 31.0%, P=0.021). Median OS for those receiving 2nd line therapy was 9 months (95% CI: 7-11 months) compared to 4 months (95% CI: 3-5 months) for those not receiving 2nd-line therapy (P<0.001). Conclusions Although likely biased due to better performance status and younger age, our patients who progressed rapidly on 1st line therapy showed an OS benefit if they received 2nd line therapy. These results suggest that patients maintaining a good PS after immediate progression on 1st line therapy should be offered 2nd line therapy.
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Affiliation(s)
- Jane E Rogers
- Pharmacy Clinical Programs, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jonathan D Mizrahi
- Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Rishi Surana
- Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Milind M Javle
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael Overman
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shubham Pant
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Investigation Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Jung HY, Lee EM. The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective analysis. Yeungnam Univ J Med 2021; 39:124-132. [PMID: 34663064 PMCID: PMC8913911 DOI: 10.12701/yujm.2021.01347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/14/2021] [Indexed: 11/28/2022] Open
Abstract
Background Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020. Results Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57–62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5–8.6 months) and 4.5 months (95% CI, 2.7–6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS. Conclusion The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.
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Affiliation(s)
- Hyun Yeb Jung
- Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan Korea
| | - Eun Mi Lee
- Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan Korea
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Abstract
Pancreatic cancer is mainly diagnosed at an advanced, often metastatic stage and still has a poor prognosis. Over the last decades, chemotherapy of metastatic pancreatic cancer (mPDAC) has proven to be superior to a mere supportive treatment with respect to both survival and quality of life. Recently, even sequential treatment of mPDAC could be established. Options for first-line treatment are combination chemotherapy regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel when the performance status of the patient is good. For patients with poorer performance status, gemcitabine single-agent treatment is a valid option. Recently, the PARP inhibitor olaparib has been demonstrated to improve progression-free survival when used as a maintenance treatment in the subgroup of patients with mPDAC and a BRCA1/-2 germ line mutation having received at least 16 weeks of platinum-based chemotherapy. This group of patients also benefits from platinum-based chemotherapy combinations. Therefore, the BRCA1/-2 stats should be examined early in patients with mPDAC even when the occurrence of these mutations is only about 5% in the general Caucasian population. After the failure of first-line treatment, patients should be offered a second-line treatment if their ECOG permits further treatment. Here, the combination of 5-FU/FA plus nanoliposomal irinotecan has shown to be superior to 5-FU/FA alone with respect to overall survival. Immune checkpoint inhibitors like PD1/PD-L1 mAbs are particularly efficacious in tumors with high microsatellite instability (MSI-h). Limited data in mPDACs shows that only a part of the already small subgroup of MSI-H mPDACs (frequency about 1%) appears to benefit substantially from a checkpoint inhibitor treatment. The identification of further subgroups, e.g., tumors with DNA damage repair deficiency, gene fusions, as well as novel approaches such as tumor-organoid-informed treatment decisions, may further improve therapeutic efficacy.
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36
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Kamgar M, Chakrabarti S, Shreenivas A, George B. Evolution of Systemic Therapy in Metastatic Pancreatic Ductal Adenocarcinoma. Surg Oncol Clin N Am 2021; 30:673-691. [PMID: 34511189 DOI: 10.1016/j.soc.2021.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Pancreatic ductal adenocarcinoma is characterized by early systemic dissemination, a complex tumor microenvironment, as well as significant intratumoral and intertumoral heterogeneity. Treatment options and survival in pancreatic ductal adenocarcinoma have improved steadily over the last 3 decades. Although cytotoxic chemotherapy is currently the mainstay of treatment for pancreatic ductal adenocarcinoma, evolving therapeutic strategies are aimed at targeting the tumor microenvironment, metabolism, and the tumor-host immune balance.
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Affiliation(s)
- Mandana Kamgar
- Division of Hematology and Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Aditya Shreenivas
- Division of Hematology and Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Ben George
- Division of Hematology and Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
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Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography. Clin Neuroradiol 2021; 32:547-556. [PMID: 34499182 PMCID: PMC9187544 DOI: 10.1007/s00062-021-01083-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/02/2021] [Indexed: 11/25/2022]
Abstract
Purpose Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose. Methods For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1–t4) with the following median and ranges in months: 3.1 (0.4–4.9), 6.2 (5.3–7.8), 10.4 (8.2–11.9), and 18.4 (12.8–49.8). Results DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08). Conclusion CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker. Supplementary Information The online version of this article (10.1007/s00062-021-01083-5) contains supplementary material, which is available to authorized users.
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Lellouche L, Palmieri LJ, Dermine S, Brezault C, Chaussade S, Coriat R. Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives. Ther Adv Med Oncol 2021; 13:17588359211018539. [PMID: 34285720 PMCID: PMC8264726 DOI: 10.1177/17588359211018539] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 04/29/2021] [Indexed: 12/25/2022] Open
Abstract
Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene (BRCA) can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients' outcomes in the near future.
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Affiliation(s)
- Lisa Lellouche
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, Paris, France
- Faculté de Médecine Paris Centre, Université de Paris, Paris, France
| | - Lola-Jade Palmieri
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, 27 rue du faubourg St Jacques, Paris, 75014, France
- Faculté de Médecine Paris Centre, Université de Paris, Paris, 75006, France
| | - Solène Dermine
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, Paris, France
- Faculté de Médecine Paris Centre, Université de Paris, Paris, France
| | - Catherine Brezault
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, Paris, France
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, Paris, France
- Faculté de Médecine Paris Centre, Université de Paris, Paris, France
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, Paris, France
- Faculté de Médecine Paris Centre, Université de Paris, Paris, France
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Imaoka H, Sasaki M, Hashimoto Y, Watanabe K, Miyazawa S, Shibuki T, Mitsunaga S, Ikeda M. Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis. Diagnostics (Basel) 2021; 11:1195. [PMID: 34209310 PMCID: PMC8307595 DOI: 10.3390/diagnostics11071195] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 02/07/2023] Open
Abstract
Precision medicine in cancer treatment refers to targeted therapy based on the evaluation of biomarkers. Although precision medicine for pancreatic cancer (PC) remains challenging, novel biomarker-based therapies, such as pembrolizumab, olaparib, and entrectinib, have been emerging. Most commonly, endoscopic ultrasound-guided tissue acquisition (EUS-TA) had been used for the diagnosis of PC until now. However, advances in EUS-TA devices and biomarker testing, especially next-generation sequencing, have opened up the possibility of sequencing of various genes even in limited amounts of tissue samples obtained by EUS-TA, and identifying potential genetic alterations as therapeutic targets. Precision medicine benefits only a small population of patients with PC, but biomarker-based therapy has shown promising results in patients who once had no treatment options. Now, the role of EUS-TA has extended beyond diagnosis into decision-making regarding the treatment of PC. In this review, we mainly discuss tissue sampling by EUS-TA for biomarker testing and the current status of precision medicine for PC.
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Affiliation(s)
- Hiroshi Imaoka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa 277-8577, Chiba, Japan; (M.S.); (Y.H.); (K.W.); (S.M.); (T.S.); (S.M.); (M.I.)
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Ikezawa K, Kiyota R, Takada R, Daiku K, Maeda S, Imai T, Abe Y, Kai Y, Yamai T, Fukutake N, Nakabori T, Ashida R, Uehara H, Tabuchi T, Katayama K, Ohkawa K. Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer. JGH Open 2021; 5:679-685. [PMID: 34124386 PMCID: PMC8171163 DOI: 10.1002/jgh3.12555] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/22/2021] [Accepted: 04/26/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM The optimal standard second-line chemotherapy for metastatic pancreatic cancer (MPC) remains unclear. Here, we evaluated the efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with oral fluoropyrimidine S-1 as a second-line chemotherapy in patients with MPC. METHODS We retrospectively reviewed 76 consecutive patients with metastatic pancreatic adenocarcinoma who underwent mFOLFIRINOX or S-1 treatment as a second-line chemotherapy after gemcitabine plus nab-paclitaxel (GnP) failure at our department between December 2014 and February 2019. RESULTS Patients who underwent mFOLFIRINOX treatment exhibited significantly better objective response rates (ORRs) and progression-free survival (PFS) than S-1 (ORR, 20.0% vs 0%, P = 0.003; PFS, 3.7 vs 2.1 months, P = 0.010). Although baseline patient characteristics of age, performance status, and serum albumin levels differed significantly between the two groups, mFOLFIRINOX was identified as an independent factor of favorable PFS on multivariate analyses. Grade 3-4 neutropenia and peripheral sensory neuropathy occurred more frequently in the mFOLFIRINOX group. The median overall survival from the initiation of second-line chemotherapy was not significantly longer in the mFOLFIRINOX group than in the S1 group (8.5 vs 5.8 months, respectively; P = 0.213); however, the 8-month survival rate was significantly higher in the mFOLFIRINOX group (56.0% vs 27.5%, respectively; P = 0.030). CONCLUSIONS mFOLFIRINOX as a second-line regimen contributed to favorable treatment outcomes, but induced more frequent adverse events than S-1. On multivariate analyses, mFOLFIRINOX was identified as an independent factor with favorable PFS, suggesting that mFOLFIRINOX could be a promising treatment option for patients with GnP failure.
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Affiliation(s)
- Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ryosuke Kiyota
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Kazuma Daiku
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Shingo Maeda
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Toshihiro Imai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yutaro Abe
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yugo Kai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Takuo Yamai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Nobuyasu Fukutake
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tasuku Nakabori
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Reiko Ashida
- Department of Cancer Survey and Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Hiroyuki Uehara
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Takahiro Tabuchi
- Cancer Control CenterOsaka International Cancer InstituteOsakaJapan
| | - Kazuhiro Katayama
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
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Cherri S, Noventa S, Zaniboni A. Pancreatic adenocarcinoma: Beyond first line, where are we? World J Gastroenterol 2021; 27:1847-1863. [PMID: 34007126 PMCID: PMC8108033 DOI: 10.3748/wjg.v27.i17.1847] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/09/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is considered one of the most aggressive cancers, with an increasing incidence in recent years. To date, chemotherapy is still the standard of care for advanced metastatic disease, unfortunately providing only a slight advantage in terms of survival. The molecular and cellular characteristics of pancreatic cancer cells, as well as the cells that characterize the pancreatic tumour microenvironment, are the basis of the mechanisms of resistance to treatment. After progression during first-line treatment, few patients are eligible for second-line treatment due to the loss of performance status. To date, a clear survival advantage has not yet been demonstrated for second-line chemotherapy. Precision medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat disease. In this review, we analyze current recommendations in the second-line setting and potential future prospects.
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Affiliation(s)
- Sara Cherri
- Department of Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Silvia Noventa
- Department of Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Alberto Zaniboni
- Department of Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
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Patterns of Palliative Chemotherapy and Survival in Patients With Pancreatic Cancer Focusing on Age: A Nationwide Real-World Danish Registry Study. Pancreas 2021; 50:685-695. [PMID: 34016900 DOI: 10.1097/mpa.0000000000001833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES The aim of this study was to identify patterns of palliative chemotherapy (CTh) and the associated overall survival (OS) in patients with pancreatic cancer, with specific focus on age. METHODS Between May 1, 2011, and April 30, 2016, 4260 patients were registered in the Danish Pancreatic Cancer Database. The 1715 patients receiving palliative CTh were retrieved. Age was grouped into less than 70, 70 to less than 75, and 75 years or more. RESULTS Of the 1715 patients receiving first-line CTh, 586 (34%) underwent second-line CTh and 151 (9%) third-line CTh. First-line gemcitabine resulted in a significant worse survival compared with combination CTh, hazard ratio 1.51. For combination CTh, OS differed between the age groups, P < 0.01. The median OS in the less than 70 years (n = 547), 70 to less than 75 years (n = 163), and 75 years or more (n = 67) groups were 9.3, 9.6, and 7.2 months, respectively. No differences in survival were observed among patients receiving first-line gemcitabine (P = 0.35). CONCLUSIONS Our findings are useful in treatment-related decision making in patients with pancreatic cancer. A significant survival benefit was observed for all patients after first-line combination CTh. The effect of combination CTh was most prominent among patients aged less than 75 years. By age, no differences in survival were observed in those receiving gemcitabine.
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Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma-Who Will Benefit from a Secondary Resection? ACTA ACUST UNITED AC 2021; 57:medicina57010077. [PMID: 33477505 PMCID: PMC7831047 DOI: 10.3390/medicina57010077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 12/31/2020] [Accepted: 01/15/2021] [Indexed: 11/18/2022]
Abstract
Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.
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Yıldırım S, Erdoğan AP, Karateke M, Yılmaz C, Özveren A, Bulut G, Ekinci F, Almuradova E. Metastatic Pancreatic Cancer Second-Line Treatment Options: Is the Difference Only in Cost? J Gastrointest Cancer 2021; 53:41-44. [PMID: 33400209 DOI: 10.1007/s12029-020-00573-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2020] [Indexed: 10/22/2022]
Abstract
İNTRODUCTION: Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity. METHODS Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined. RESULTS Our study's primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens. CONCLUSION As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.
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Affiliation(s)
- Serkan Yıldırım
- Department Of Medical Oncology, Bitlis Tatvan Public Hospital, Tatvan, 13200, Bitlis, Turkey.
| | - A P Erdoğan
- Celal Bayar University Medical School, Manisa, Turkey
| | - M Karateke
- Ege University Medical School, Izmir, Turkey
| | - C Yılmaz
- İzmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | | | - G Bulut
- Hatay Defne Hospital, Hatay, Turkey
| | - F Ekinci
- Celal Bayar University Medical School, Manisa, Turkey
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Yu S, Zhang C, Xie KP. Therapeutic resistance of pancreatic cancer: Roadmap to its reversal. Biochim Biophys Acta Rev Cancer 2020; 1875:188461. [PMID: 33157162 DOI: 10.1016/j.bbcan.2020.188461] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/20/2020] [Accepted: 10/24/2020] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease.
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Affiliation(s)
- Sen Yu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China
| | - Chunyu Zhang
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China
| | - Ke-Ping Xie
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China.
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Schultheis B, Strumberg D, Kuhlmann J, Wolf M, Link K, Seufferlein T, Kaufmann J, Feist M, Gebhardt F, Khan M, Stintzing S, Pelzer U. Safety, Efficacy and Pharcacokinetics of Targeted Therapy with The Liposomal RNA Interference Therapeutic Atu027 Combined with Gemcitabine in Patients with Pancreatic Adenocarcinoma. A Randomized Phase Ib/IIa Study. Cancers (Basel) 2020; 12:E3130. [PMID: 33114652 PMCID: PMC7693593 DOI: 10.3390/cancers12113130] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/05/2020] [Accepted: 10/18/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences the expression of protein kinase N3 (PKN3) in the vascular endothelium. This trial was designed to assess the safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). METHODS In total, 23 patients (pts) with inoperable APC were randomly assigned to gemcitabine combined with two different Atu027 schedules (0.235 mg/kg once weekly vs. 0.235 mg/kg twice weekly). ClinicalTrials.gov Identifier: NCT01808638. RESULTS The treatment was well-tolerated. There were Grade 3 adverse events (AEs) in 9/11 pts (arm 1) and 11/12 pts (arm 2), while Grade 4 AEs were reported for two pts in each arm. The AEs were mainly laboratory abnormalities without clinical significance. The median progression-free survival reached statistical significance in patients who had metastatic disease (1.6 vs. 2.9 months, p = 0.025). Disease control during treatment was achieved in 4/11 pts (arm 1) and in 7/12 pts (arm 2). Pts in arm 1 experienced stable global health status while pts in arm 2 reported improvement. CONCLUSIONS Combining Atu027 with gemcitabine is safe and well tolerated. In pts with metastatic APC, twice-weekly Atu027 is associated with significantly improved outcomes. Our clinical results support the significant involvement of the vascular endothelium in the spread of cancer, and thus the further investigation of its target role.
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Affiliation(s)
- Beate Schultheis
- Department of Hematology and Oncology, Marien Hospital Herne, University of Bochum, 44627 Herne, Germany; (B.S.); (D.S.)
| | - Dirk Strumberg
- Department of Hematology and Oncology, Marien Hospital Herne, University of Bochum, 44627 Herne, Germany; (B.S.); (D.S.)
| | - Jan Kuhlmann
- Department of Medicine II, University Hospital Freiburg, 79106 Freiburg, Germany;
| | - Martin Wolf
- Department of Medicine, Hospital Kassel, 34125 Kassel, Germany;
| | - Karin Link
- Department of Medicine V, Hospital Nuernberg Nord, 90419 Nuernberg, Germany;
| | | | - Joerg Kaufmann
- Silence Therapeutics GmbH, 13125 Berlin, Germany; (J.K.); (F.G.)
| | - Mathilde Feist
- Department of Surgery, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
- Medical faculty, Humboldt-Universität zu Berlin, 10099 Berlin, Germany
- Berlin Institute of Health, 10178 Berlin, Germany
| | - Frank Gebhardt
- Silence Therapeutics GmbH, 13125 Berlin, Germany; (J.K.); (F.G.)
| | - Mike Khan
- Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK;
| | - Sebastian Stintzing
- Medical faculty, Humboldt-Universität zu Berlin, 10099 Berlin, Germany
- Berlin Institute of Health, 10178 Berlin, Germany
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Uwe Pelzer
- Medical faculty, Humboldt-Universität zu Berlin, 10099 Berlin, Germany
- Berlin Institute of Health, 10178 Berlin, Germany
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
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Catalano M, Conca R, Petrioli R, Ramello M, Roviello G. FOLFOX vs FOLFIRI as Second-line of Therapy After Progression to Gemcitabine/Nab-paclitaxel in Patients with Metastatic Pancreatic Cancer. Cancer Manag Res 2020; 12:10271-10278. [PMID: 33116881 PMCID: PMC7585276 DOI: 10.2147/cmar.s267393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/24/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Several progresses have been achieved for first-line chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with Gem-NabP and FOLFIRINOX extensively used as standard first line regimens. However, the best second-line chemotherapy choice after progression is still not completely defined. The aim of this study is to compare effectiveness and safety of two possible second-line therapeutic options, FOLFOX and FOLFIRI, after progression to Gem-NabP. METHODS From January 2015 to December 2018, patients with metastatic PDAC, progressed to the first-line treatment with Gem-NabP, and treated with a fluoropyrimidine-based second-line chemotherapy were considered eligible for our retrospective analysis. Overall survival (OS) and progression free survival (PFS) were set as primary endpoints whereas, disease control rate (DCR) and the rate and severity of treatment-related AEs were secondary endpoints. RESULTS Overall, 31 patients were treated with Gem-NabP in first-line regimen, 11 received second-line with FOLFOX and 20 with FOLFIRI after progression. Baseline demographic and clinic features were similar in the two groups excluding median age of 55.5 years (range: 50-73) and 68 years (range: 59-72) in FOLFIRI and FOLFOX groups, respectively (p=0.002). Median PFS was three months (95%CI: 3-4), with no significative difference between the two groups. Median OS was eight months (95%CI: 5-10) and was significantly higher in the FOLFIRI group compared with the FOLFOX group, nine months (95%CI: 7-17) vs five months (95%CI: 2-10; p<0.01). The most commonly reported adverse events were grade 1 or 2 with anemia most frequent in the FOLFOX group (36.4% vs 10.0%) and diarrhea in the FOLFIRI group (40.0% vs 9.1%). Grade 3-4 adverse events as neutropenia, diarrhea and nausea/vomiting, occurred in 10 patients (32.2%) without differences between the two groups. CONCLUSION Our results seem to support the use of fluoropyrimidine-based second-line therapy for patients with metastatic pancreatic cancer, confirming the effectiveness and safety, to a greater extent with FOLFIRI regimen, after progression to the Gem-NabP.
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Affiliation(s)
- Martina Catalano
- School of Human Health Sciences, University of Florence, Florence50134, Italy
| | - Raffaele Conca
- Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero, Vulture (PZ)85028, Italy
| | - Roberto Petrioli
- Department of Medicine, Surgery and Neurosciences, Medical Oncology Unit, University of Siena, Siena53100, Italy
| | - Monica Ramello
- Oncology Unit, Department of Medical, Surgical, & Health Sciences, University of Trieste, Trieste, Italy
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Body A, Wong R, Shapiro J, Jalali A, McLachlan S, Ananda S, Lipton L, Cooray P, Gibbs P, Lee B, Lee M. Use and outcomes of chemotherapy for metastatic pancreatic cancer in Australia. Intern Med J 2020; 52:49-56. [DOI: 10.1111/imj.15094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/04/2020] [Accepted: 10/07/2020] [Indexed: 11/30/2022]
Affiliation(s)
- Amy Body
- Department of Medical Oncology Eastern Health Melbourne Australia
| | - Rachel Wong
- Department of Medical Oncology Eastern Health Melbourne Australia
- Eastern Health Clinical School Monash University Melbourne Australia
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
| | - Jeremy Shapiro
- Department of Medical Oncology Cabrini Hospital Melbourne Australia
| | - Azim Jalali
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
- Department of Medical Oncology Western Health Melbourne Australia
| | - Sue‐Anne McLachlan
- Department of Medical Oncology St Vincent's Hospital Melbourne Australia
- Faculty of Medicine and Health Sciences University of Melbourne Australia
| | - Sumitra Ananda
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
- Department of Medical Oncology Epworth Freemasons' Hospital Melbourne Australia
- Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Australia
- Faculty of Medicine and Health Sciences University of Melbourne Australia
| | - Lara Lipton
- Department of Medical Oncology Cabrini Hospital Melbourne Australia
- Department of Medical Oncology Western Health Melbourne Australia
- Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Australia
| | - Prasad Cooray
- Department of Medical Oncology Knox Private Hospital Melbourne Australia
- Faculty of Medicine and Health Sciences University of Melbourne Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
- Department of Medical Oncology Western Health Melbourne Australia
- Faculty of Medicine and Health Sciences University of Melbourne Australia
| | - Belinda Lee
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
- Department of Medical Oncology Northern Health Melbourne Australia
- Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Australia
- Faculty of Medicine and Health Sciences University of Melbourne Australia
| | - Margaret Lee
- Department of Medical Oncology Eastern Health Melbourne Australia
- Eastern Health Clinical School Monash University Melbourne Australia
- Walter and Eliza Hall Institute of Medical Research Melbourne Australia
- Department of Medical Oncology Western Health Melbourne Australia
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Hsu CC, Liu KH, Chang PH, Chen PT, Hung CY, Hsueh SW, Yeh KY, Chen YY, Lu CH, Hung YS, Chou WC. Development and validation of a prognostic nomogram to predict survival in patients with advanced pancreatic cancer receiving second-line palliative chemotherapy. J Gastroenterol Hepatol 2020; 35:1694-1703. [PMID: 31711261 DOI: 10.1111/jgh.14926] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/31/2019] [Accepted: 11/02/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Given that a wide variation in tumor response rates and survival times suggests heterogeneity among the patients with advanced pancreatic cancer (APC) who underwent second-line (L2) chemotherapy, it is a challenge in clinical practice to identify patients who will receive the most benefit from L2 treatment. METHODS We selected 183 APC patients who received L2 palliative chemotherapy between 2010 and 2016 from a medical center as the development cohort. A Cox proportional hazard model was used to identify the prognostic factors and construct the nomogram. An independent cohort of 166 patients from three other hospitals was selected for external validation. RESULTS The nomogram was based on eight independent prognostic factors from the multivariate Cox model: sex, Eastern Cooperative Oncology Group performance status, reason for first-line treatment discontinuation, duration of first-line treatment, neutrophil-to-lymphocyte ratio, tumor stage, body mass index, and serum carbohydrate antigen 19-9 levels at the beginning of L2 treatment. The model exhibited good discrimination ability, with a C-index of 0.733 (95% confidence interval, 0.681-0.785) and 0.724 (95% confidence interval, 0.661-0.787) in the development and validation cohorts, respectively. The calibration plots of the development and validation cohorts showed optimal agreement between model prediction and actual observation in predicting survival probability at 6 months, 1 year, and 2 years. CONCLUSIONS This study developed and externally validated a prognostic model that accurately predicts the survival outcome of APC patients before L2 palliative chemotherapy, which could assist in clinical decision-making, counseling for treatment, and most importantly, prognostic stratification of patients.
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Affiliation(s)
- Chih-Chung Hsu
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Keng-Hao Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Hung Chang
- Department of Oncology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan
| | - Ping-Tsung Chen
- Department of Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Chia-Yen Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Hema-oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Shun-Wen Hsueh
- Department of Oncology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan
| | - Kun-Yun Yeh
- Department of Oncology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan
| | - Yen-Yang Chen
- Department of Oncology, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan
| | - Chang-Hsien Lu
- Department of Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Yu-Shin Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wen-Chi Chou
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Bachet JB, Blons H, Hammel P, Hariry IE, Portales F, Mineur L, Metges JP, Mulot C, Bourreau C, Cain J, Cros J, Laurent-Puig P. Circulating Tumor DNA is Prognostic and Potentially Predictive of Eryaspase Efficacy in Second-line in Patients with Advanced Pancreatic Adenocarcinoma. Clin Cancer Res 2020; 26:5208-5216. [PMID: 32605910 DOI: 10.1158/1078-0432.ccr-20-0950] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/13/2020] [Accepted: 06/25/2020] [Indexed: 11/16/2022]
Abstract
PURPOSE Eryaspase is composed of l-asparaginase encapsulated in erythrocytes and has demonstrated significant efficacy in a randomized phase II trial. We assessed the prognostic and predictive value of circulating tumor DNA (ctDNA) in patients, plasma included in this trial. EXPERIMENTAL DESIGN Samples prospectively collected pretreatment were centrally analyzed by next-generation sequencing. Prognostic values of baseline ctDNA and ctDNA early changes between day 0 and 28 were assessed in both arms combined on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS); three groups were defined: negative ctDNA (Neg), ctDNA responders (Resp), and ctDNA nonresponders (NResp). Predictive value of ctDNA for eryaspase efficacy was investigated. RESULTS ctDNA was positive at baseline in 77 patients of the 113 tested patients (68%). Detectable ctDNA was an independent negative prognostic factor for OS (4.6 vs. 8.8 months; P = 0.0025) and PFS (1.6 vs. 3.3 months; P = 0.00043). Early change in ctDNA levels was correlated with ORR (20%, 26%, 0%; P < 0.04), PFS (3.7, 3.4, 1.6 months; P < 0.0001), and OS (11.7, 6.5, 4.3 months; P < 0.0001) according to the three defined groups (Neg, Res, NResp, respectively). In patients with ctDNA detectable at baseline, eryaspase was associated with better PFS [HR = 0.53; 95% confidence interval (CI): 0.3-0.94)] and OS (HR = 0.52; 95% CI: 0.29-0.91). CONCLUSIONS We confirm from a prospective randomized trial that: (i) the presence of ctDNA at baseline is a major prognostic factor, (ii) the early change of ctDNA correlates with treatment outcome, and (iii) the ctDNA could be a predictive biomarker of eryaspase efficacy.
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Affiliation(s)
- Jean-Baptiste Bachet
- Sorbonne Université, UPMC Université, IUC, Paris, France
- Assistance Publique-Hôpitaux de Paris, Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France
- Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France
| | - Hélène Blons
- Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France
- Assistance Publique-Hôpitaux de Paris, Department of Biochemistry, Hôpital Européen Georges Pompidou, Paris, France
| | - Pascal Hammel
- Assistance Publique-Hôpitaux de Paris, Université de Paris, Medical Oncology Unit, Hôpital Beaujon, Clichy, France
| | | | | | - Laurent Mineur
- Institut Sainte Catherine, Gastrointestinal and Liver Cancer Unit, Chemin de baigne pieds, Avignon, France
| | | | - Claire Mulot
- Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France
- Biological Ressources Center Epigenetec (BB-0033-00055), INSERM, Université de Paris, Paris, France
| | - Camille Bourreau
- Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France
- Biological Ressources Center Epigenetec (BB-0033-00055), INSERM, Université de Paris, Paris, France
| | | | - Jérôme Cros
- Assistance Publique-Hôpitaux de Paris, INSERM, Paris University, Department of Pathology Hôpital Beaujon, Clichy, France
| | - Pierre Laurent-Puig
- Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France.
- Assistance Publique-Hôpitaux de Paris, Department of Biochemistry, Hôpital Européen Georges Pompidou, Paris, France
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