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Cardoso VDO, Bistaffa MJ, Sterman RG, Lima LLD, Toldo GS, Cancino-Bernardi J, Zucolotto V. Nanomedicine Innovations for Lung Cancer Diagnosis and Therapy. ACS APPLIED MATERIALS & INTERFACES 2025; 17:13197-13220. [PMID: 40045524 PMCID: PMC11891907 DOI: 10.1021/acsami.4c16840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 03/12/2025]
Abstract
Lung cancer remains a challenge within the realm of oncology. Characterized by late-stage diagnosis and resistance to conventional treatments, the currently available therapeutic strategies encompass surgery, radiotherapy, chemotherapy, immunotherapy, and biological therapy; however, overall patient survival remains suboptimal. Nanotechnology has ushered in a new era by offering innovative nanomaterials with the potential to precisely target cancer cells while sparing healthy tissues. It holds the potential to reshape the landscape of cancer management, offering hope for patients and clinicians. The assessment of these nanotechnologies follows a rigorous evaluation process similar to that applied to chemical drugs, which includes considerations of their pharmacokinetics, pharmacodynamics, toxicology, and clinical effectiveness. However, because of the characteristics of nanoparticles, standard toxicological tests require modifications to accommodate their unique characteristics. Effective therapeutic strategies demand a profound understanding of the disease and consideration of clinical outcomes, physicochemical attributes of nanomaterials, nanobiointeractions, nanotoxicity, and regulatory compliance to ensure patient safety. This review explores the promise of nanomedicine in lung cancer treatment by capitalizing on its unique physicochemical properties. We address the multifaceted challenges of lung cancer and its tumor microenvironment and provide an overview of recent developments in nanoplatforms for early diagnosis and treatment that can enhance patient outcomes and overall quality of life.
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Affiliation(s)
- Valéria
Maria de Oliveira Cardoso
- Nanomedicine
and Nanotoxicology Group, São Carlos Institute of Physics, University of São Paulo, 13560-970 São Carlos, São Paulo, Brazil
| | - Maria Julia Bistaffa
- Nanomedicine
and Nanotoxicology Group, São Carlos Institute of Physics, University of São Paulo, 13560-970 São Carlos, São Paulo, Brazil
| | - Raquel González Sterman
- Nanomedicine
and Nanotoxicology Group, São Carlos Institute of Physics, University of São Paulo, 13560-970 São Carlos, São Paulo, Brazil
| | - Lorena Leticia
Peixoto de Lima
- Nanomedicine
and Nanotoxicology Group, São Carlos Institute of Physics, University of São Paulo, 13560-970 São Carlos, São Paulo, Brazil
| | - Gustavo Silveira Toldo
- Chemistry
Department, Laboratory in Bioanalytical of Nanosystems, Faculty of
Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, 14040-901 Ribeirão Preto, São Paulo, Brazil
| | - Juliana Cancino-Bernardi
- Chemistry
Department, Laboratory in Bioanalytical of Nanosystems, Faculty of
Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, 14040-901 Ribeirão Preto, São Paulo, Brazil
| | - Valtencir Zucolotto
- Nanomedicine
and Nanotoxicology Group, São Carlos Institute of Physics, University of São Paulo, 13560-970 São Carlos, São Paulo, Brazil
- Comprehensive
Center for Precision Oncology, C2PO, University of São Paulo, São Paulo 01246-000, Brazil
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Tang J, Wang T, Wu H, Bao X, Xu K, Ren T. Efficacy and toxicity of lurbinectedin in subsequent systemic therapy of extensive-stage small cell lung cancer: a meta-analysis. BMC Cancer 2024; 24:1351. [PMID: 39497053 PMCID: PMC11533368 DOI: 10.1186/s12885-024-13104-w] [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: 07/11/2024] [Accepted: 10/24/2024] [Indexed: 11/06/2024] Open
Abstract
OBJECTIVE This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). METHODS Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. RESULTS Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29-41), DCR was 67% (95%CI 58-76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11-9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78-100) and 37% (95%CI 19-57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68-91), 74% (57-88), 73% (35-98) and 57% (46-68), respectively. CONCLUSION As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation.
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Affiliation(s)
- Jiayi Tang
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Tianlei Wang
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Hongwei Wu
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Xinrui Bao
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Ke Xu
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China.
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
| | - Tao Ren
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China.
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
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Byrne MM, Sutamtewagul G, Zeitler W, Mott SL, Zamba GK, Kojadinovic A, Zhang J, Abu-Hejleh T, Clamon G, Furqan M. Phase II study of nab-paclitaxel with gemcitabine for relapsed/refractory small cell lung cancer. Front Oncol 2024; 14:1303268. [PMID: 39144826 PMCID: PMC11322450 DOI: 10.3389/fonc.2024.1303268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 04/08/2024] [Indexed: 08/16/2024] Open
Abstract
Background Patients with small cell lung cancer (SCLC) often respond to first-line chemoimmunotherapy. However, relapse is inevitable and is associated with a poor prognosis. Treatments for relapsed SCLC, such as lurbinectedin and topotecan, are limited by modest efficacy and significant hematologic adverse events, leaving a need for newer therapeutic agents or regimens. The combination of gemcitabine and nab-paclitaxel is active and safe in other types of malignancies, such as pancreatic cancer. Patients and methods We conducted a phase II trial evaluating the efficacy and safety of gemcitabine and nab-paclitaxel in patients with relapsed/refractory SCLC. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial response. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. Results Between October 2016 and May 2021, 32 patients were enrolled. Patients were followed for a median of 9.3 months (range 1.8-65.2). Median age was 65 years (range 48-81). Fifty percent of patients were female. Fifty-three percent of patients had platinum-resistant/refractory relapsed SCLC. The ORR was 28.1% (95% confidence interval [CI] 15.5-100%). Median PFS was 2.9 months (95% CI 2.4-3.6), and median OS was 9.3 months (95% CI 5.2-12.4). Seven patients (21.9%) developed grade 3 or 4 neutropenia. Conclusion Our study showed that the combination of gemcitabine and nab-paclitaxel led to encouraging outcomes in relapsed/refractory SCLC. Further studies are needed to compare this combination with other treatments used for relapsed SCLC, including lurbinectedin, temozolomide, and topotecan. Clinical trial registration https://clinicaltrials.gov/study/NCT02769832?cond=NCT02769832&rank=1, identifier NCT02769832.
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Affiliation(s)
- Margaret M. Byrne
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Grerk Sutamtewagul
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - William Zeitler
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Sarah L. Mott
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
| | - Gideon K.D. Zamba
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
- Department of Biostatistics, University of Iowa, Iowa City, IA, United States
| | - Arsenije Kojadinovic
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Jun Zhang
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Taher Abu-Hejleh
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Gerald Clamon
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
| | - Muhammad Furqan
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
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Sands J, Subramanian J. Treating patients with platinum-sensitive extensive-stage small-cell lung cancer in a real-world setting. Front Oncol 2023; 13:1161931. [PMID: 38221913 PMCID: PMC10786446 DOI: 10.3389/fonc.2023.1161931] [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: 02/08/2023] [Accepted: 10/09/2023] [Indexed: 01/16/2024] Open
Abstract
Extensive-stage small-cell lung cancer (ES-SCLC) is an aggressive disease with poor 5-year survival. The first-line standard-of-care for ES-SCLC is platinum plus etoposide, along with 1 of the immune checkpoint inhibitors atezolizumab or durvalumab. Although SCLC first-line therapy often leads to rapid responses, treatment becomes more challenging at progression, particularly for those with a chemotherapy-free interval (CTFI) of ≤6 months. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for SCLC no longer specify treatment recommendations in this setting, but options approved by the US Food and Drug Administration include topotecan and lurbinectedin. Participation in a clinical trial is recommended as an option regardless of CTFI. Other NCCN-recommended regimens are paclitaxel, irinotecan, temozolomide, and cyclophosphamide/doxorubicin/vincristine, among others. Nivolumab and pembrolizumab are options in those not previously treated with a checkpoint inhibitor. For patients with platinum-sensitive SCLC (CTFI >6 months), preferred treatment per the NCCN Guidelines® for SCLC is retreatment with platinum and etoposide, although the use of immune checkpoint inhibitors is discouraged if there is progression on a drug in this class. Further research on immunotherapies and combination regimens is ongoing, and continuing work on the subcharacterization of SCLC may lead to better precision of therapies that promote more durable responses in individual patients with ES-SCLC.
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Affiliation(s)
- Jacob Sands
- Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
| | - Janakiraman Subramanian
- Division of Oncology, Saint Luke’s Cancer Institute, Kansas City, MO, United States
- Center for Precision Oncology, Saint Luke’s Cancer Institute, Kansas City, MO, United States
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Khurshid H, Ismaila N, Bian J, Dabney R, Das M, Ellis P, Feldman J, Hann C, Kulkarni S, Laskin J, Manochakian R, Mishra DR, Preeshagul I, Reddy P, Saxena A, Weinberg F, Kalemkerian GP. Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline. J Clin Oncol 2023; 41:5448-5472. [PMID: 37820295 DOI: 10.1200/jco.23.01435] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/17/2023] [Accepted: 07/20/2023] [Indexed: 10/13/2023] Open
Abstract
PURPOSE To provide evidence-based recommendations to practicing clinicians on the management of patients with small-cell lung cancer. METHODS An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2022. Outcomes of interest included response rates, overall survival, disease-free survival or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 95 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed to address systemic therapy options, timing of therapy, treatment in patients who are older or with poor performance status, role of biomarkers, and use of myeloid-supporting agents in patients with small-cell lung cancer.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
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Affiliation(s)
| | - Nofisat Ismaila
- American Society of Clinical Oncology (ASCO), Alexandria, VA
| | | | | | | | - Peter Ellis
- Juravinski Cancer Center, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Jill Feldman
- EGFR Resisters Patient Advocacy Group, Deerfield, IL
| | | | - Swati Kulkarni
- Western University, Windsor Regional Cancer Program, Windsor, Ontario, Canada
| | - Janessa Laskin
- University of British Columbia, Vancouver, British Columbia, Canada
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Melosky BL, Leighl NB, Dawe D, Blais N, Wheatley-Price PF, Chu QSC, Juergens RA, Ellis PM, Sun A, Schellenberg D, Ionescu DN, Cheema PK. Canadian Consensus Recommendations on the Management of Extensive-Stage Small-Cell Lung Cancer. Curr Oncol 2023; 30:6289-6315. [PMID: 37504325 PMCID: PMC10378571 DOI: 10.3390/curroncol30070465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/27/2023] [Accepted: 06/29/2023] [Indexed: 07/29/2023] Open
Abstract
Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC). The literature search included guidelines, systematic reviews, and randomized controlled trials. Regular meetings were held from September 2022 to March 2023 to discuss the available evidence to propose and agree upon specific recommendations. The panel addressed biomarkers and histological features that distinguish SCLC from non-SCLC and other neuroendocrine tumours. Evidence for initial and subsequent systemic therapies was reviewed with consideration for patient performance status, comorbidities, and the involvement and function of other organs. The resulting consensus recommendations herein will help clarify evidence-based management of ES-SCLC in routine practice, help clinician decision-making, and facilitate the best patient outcomes.
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Affiliation(s)
- Barbara L. Melosky
- Department of Medical Oncology, BC Cancer-Vancouver Centre, Vancouver, BC V5Z 4E6, Canada
| | - Natasha B. Leighl
- Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5S 1A8, Canada;
| | - David Dawe
- CancerCare Manitoba Research Institute, CancerCare Manitoba, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0V9, Canada;
| | - Normand Blais
- Department of Medicine, Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, QC H2X 3E4, Canada;
| | - Paul F. Wheatley-Price
- Department of Medicine, The Ottawa Hospital Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8L6, Canada;
| | - Quincy S.-C. Chu
- Division of Medical Oncology, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada;
| | - Rosalyn A. Juergens
- Department of Medical Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada;
| | - Peter M. Ellis
- Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada;
| | - Alexander Sun
- Princess Margaret Cancer Centre, Radiation Medicine Program, University Health Network, Toronto, ON M5G 2M9, Canada;
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5G 2M9, Canada
| | - Devin Schellenberg
- Department of Radiation Oncology, BC Cancer—Surrey Centre, 13750 96 Avenue, Surrey, BC V3V 1Z2, Canada;
| | - Diana N. Ionescu
- Department of Pathology, BC Cancer, Vancouver, BC V5Z 4E6, Canada;
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada
| | - Parneet K. Cheema
- Division of Medical Oncology, William Osler Health System, University of Toronto, Brampton, ON L6R 3J7, Canada;
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
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Wan R, Guo Y, Hao X, Wang Z, Duan J, Wang J. Efficacy and safety of nab-paclitaxel or combined nab-paclitaxel and immune checkpoint inhibitors in relapsed small-cell lung cancer. Ther Adv Med Oncol 2023; 15:17588359231179315. [PMID: 37389188 PMCID: PMC10302613 DOI: 10.1177/17588359231179315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/11/2023] [Indexed: 07/01/2023] Open
Abstract
Background Most patients with small-cell lung cancer (SCLC) experience disease progression after first-line chemotherapy. Notably, nab-paclitaxel monotherapy has antitumor activity in relapsed SCLC. Objective This study evaluated the efficacy and safety of combined of nab-paclitaxel and immune checkpoint inhibitors (ICIs) in relapsed SCLC. Design We retrospectively analyzed patients with relapsed SCLC who received nab-paclitaxel or combined nab-paclitaxel and ICIs (anti-programmed death-1, PD-1 or anti-programmed cell death 1 ligand, PD-L1) between February 2017 and September 2021. Methods Efficacy and safety data were collected from electronic health records. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and a standard log-rank test. Results We included 56 patients with relapsed SCLC, of which 29 received nab-paclitaxel alone (Group A), and 27 received combined nab-paclitaxel and ICIs (Group B). Baseline characteristics were similar between the two groups. Group B had a numerically higher objective response rate than Group A (40.7% versus 17.2%; p = 0.052). However, combined nab-paclitaxel and ICIs failed to demonstrate survival superiority over nab-paclitaxel monotherapy [median PFS: 3.2 months versus 2.8 months (p = 0.5225); median OS: 11.0 months versus 9.3 months (p = 0.7298)]. The safety profiles of Groups A and B were both tolerable. Conclusion This study indicated that compared with nab-paclitaxel monotherapy, combined nab-paclitaxel and ICIs failed to improve survival in relapsed SCLC.
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Affiliation(s)
- Rui Wan
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanrong Guo
- Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Xuezhi Hao
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhijie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianchun Duan
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Wang
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan Nanli N0.17, Beijing, 100021, China
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Roussel-Simonin C, Gougis P, Lassoued D, Vozy A, Veyri M, Morardet L, Wassermann J, Foka Tichoue H, Jaffrelot L, Hassani L, Perrier A, Bergeret S, Taillade L, Spano JP, Campedel L, Abbar B. FOLFIRI in advanced platinum-resistant/refractory small-cell lung cancer: a retrospective study. Acta Oncol 2023:1-8. [PMID: 37276270 DOI: 10.1080/0284186x.2023.2216339] [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: 03/20/2023] [Accepted: 05/11/2023] [Indexed: 06/07/2023]
Abstract
BACKGROUND Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancer and is associated with poor prognosis. In platinum-refractory or -resistant SCLC patients, few treatment options are available. Topotecan is one of the standards of care for these patients, however, due to its high toxicity, several different approaches are employed. FOLFIRI (folinate, 5-fluorouracil and irinotecan) is a chemotherapy regimen used in digestive neuroendocrine carcinoma, which shares pathological similarities with SCLC. In this retrospective study, we evaluated the efficacy and safety of FOLFIRI in patients with platinum-resistant/refractory SCLC. METHODS Medical records from all consecutive SCLC patients treated with FOLFIRI in a French University Hospital from 2013 to 2021 were analyzed retrospectively. The primary endpoint was the objective response rate according to RECIST v1.1 or EORTC criteria (ORR); secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS) and safety profile. RESULTS Thirty-four patients with metastatic platinum-resistant (n = 14) or -refractory (n = 20) SCLC were included. Twenty-eight were evaluable for response, with a partial response observed in 5 patients for an overall ORR in the evaluable population of 17.9% (5/28) and 14.7% (5/34) in the overall population. The disease control rate was 50% (14/28) in the evaluable population. The median PFS and OS were 2.8 months (95%CI, 2.0-5.2 months) and 5.3 months (95%CI, 3.5-8.9 months), respectively. All patients were included in the safety analysis. Grade 3 or 4 adverse events occurred in 13 (38.2%) patients. The most common grade 3 or 4 adverse events were asthenia, neutropenia, thrombopenia and diarrhea. There was no adverse event leading to discontinuation or death. CONCLUSION FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response and had an acceptable safety profile. However, caution is needed in interpreting this result. FOLFIRI could represent a potential new treatment for platinum-resistant/refractory SCLC patients. Further prospective studies are needed to assess the benefits of this chemotherapy regimen.HIGHLIGHTSFOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response.FOLFIRI was well-tolerated in platinum resistant/refractory SLCL patients.FOLFIRI could represent a potential new treatment for SCLC, prospective studies are needed.
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Affiliation(s)
- Cyril Roussel-Simonin
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Paul Gougis
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
- Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Paris, France
| | - Donia Lassoued
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Aurore Vozy
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
- Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm U1135, Paris, France
| | - Marianne Veyri
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut Universitaire de Cancérologie, CLIP2 Galilée, Paris, France
| | - Laetitia Morardet
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Johanna Wassermann
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Hervé Foka Tichoue
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Loïc Jaffrelot
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Lamia Hassani
- Department of Pharmacy, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Alexandre Perrier
- Sorbonne Université, Département de Génétique Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Sebastien Bergeret
- Sorbonne Université, Département de Médecine Nucléaire, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Laurent Taillade
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Jean-Philippe Spano
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut Universitaire de Cancérologie, CLIP2 Galilée, Paris, France
| | - Luca Campedel
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
| | - Baptiste Abbar
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Paris, France
- Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm U1135, Paris, France
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9
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Pangua C, Rogado J, Serrano-Montero G, Belda-Sanchís J, Álvarez Rodríguez B, Torrado L, Rodríguez De Dios N, Mielgo-Rubio X, Trujillo JC, Couñago F. New perspectives in the management of small cell lung cancer. World J Clin Oncol 2022; 13:429-447. [PMID: 35949427 PMCID: PMC9244973 DOI: 10.5306/wjco.v13.i6.429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 09/05/2021] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
The treatment of small cell lung cancer (SCLC) is a challenge for all specialists involved. New treatments have been added to the therapeutic armamentarium in recent months, but efforts must continue to improve both survival and quality of life. Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications, while more careful patient selection has led to increased staging accuracy. Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease, mainly with the introduction of immunotherapy. In this article, we describe recent improvements in the management of patients with SCLC, review current treatments, and discuss future lines of research.
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Affiliation(s)
- Cristina Pangua
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - Jacobo Rogado
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - Gloria Serrano-Montero
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - José Belda-Sanchís
- Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau & Hospital de Mar, Universitat Autònoma de Barcelona, Barcelona 08041, Catalonia, Spain
| | - Beatriz Álvarez Rodríguez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, HM CIOCC Centro Integral Oncológico Clara Campal, Madrid 28050, Spain
| | - Laura Torrado
- Department of Radiation Oncology, Hospital Universitario Lucus Augusti & Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), Lugo 27003, Spain
| | - Nuria Rodríguez De Dios
- Department of Radiation Oncology, Hospital Del Mar & Hospital Del Mar Medical Research Institute (IMIM) & Pompeu Fabra University, Barcelona 08003, Catalonia, Spain
| | - Xabier Mielgo-Rubio
- Department of Medical Oncology, Alcorcón Foundation University Hospital, Alcorcón 28922, Madrid, Spain
| | - Juan Carlos Trujillo
- Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona 08029, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Spain
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10
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Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D'Amico TA, D'Avella C, Dowlati A, Downey RJ, Edelman M, Florsheim C, Gold KA, Goldman JW, Grecula JC, Hann C, Iams W, Iyengar P, Kelly K, Khalil M, Koczywas M, Merritt RE, Mohindra N, Molina J, Moran C, Pokharel S, Puri S, Qin A, Rusthoven C, Sands J, Santana-Davila R, Shafique M, Waqar SN, Gregory KM, Hughes M. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:1441-1464. [PMID: 34902832 DOI: 10.6004/jnccn.2021.0058] [Citation(s) in RCA: 234] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The "Summary of the Guidelines Updates" section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.
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Affiliation(s)
| | | | | | | | | | | | | | - Afshin Dowlati
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | | | - John C Grecula
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Christine Hann
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Robert E Merritt
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Nisha Mohindra
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Cesar Moran
- The University of Texas MD Anderson Cancer Center
| | | | - Sonam Puri
- Huntsman Cancer Institute at the University of Utah
| | - Angel Qin
- University of Michigan Rogel Cancer Center
| | | | - Jacob Sands
- Dana Farber/Brigham and Women's Cancer Center
| | | | | | - Saiama N Waqar
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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11
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Fujita K, Nakao M, Arakawa S, Sone K, Sato H, Muramatsu H. Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure. J Rural Med 2021; 16:250-255. [PMID: 34707735 PMCID: PMC8527629 DOI: 10.2185/jrm.2021-014] [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: 03/24/2021] [Accepted: 07/01/2021] [Indexed: 11/27/2022] Open
Abstract
Objective: The utility of topotecan monotherapy for relapsed small-cell lung
cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to
investigate the efficacy and safety of topotecan monotherapy in patients with relapsed
SCLC after amrubicin monotherapy. Patients and Methods: We retrospectively analyzed data from 16 patients with
relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at
our hospital. Results: The response rate, progression-free survival, and overall survival
were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267),
respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and
thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections. Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after
amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.
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Affiliation(s)
- Kohei Fujita
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
| | - Makoto Nakao
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
| | - Sosuke Arakawa
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
| | - Kazuki Sone
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
| | - Hidefumi Sato
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
| | - Hideki Muramatsu
- Department of Respiratory Medicine, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Japan
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12
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Future Perspective of Chemotherapy and Pharmacotherapy in Thymic Carcinoma. Cancers (Basel) 2021; 13:cancers13205239. [PMID: 34680386 PMCID: PMC8533972 DOI: 10.3390/cancers13205239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/07/2021] [Accepted: 10/09/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Thymic carcinoma is a rare cancer, and its biology remains largely unknown. Although complete surgical resection is a standard treatment for thymic carcinoma, systemic chemotherapy is frequently administered in metastatic or recurrent cases. Given the rarity, therapeutic agents are often confirmed on the basis of the results of phase II trials or retrospective studies. Platinum-based combination chemotherapy has long been employed for treating thymic carcinoma. Recently, biomarkers have been explored, and molecular profiles and major oncogenic pathways have gradually been revealed by next-generation sequencing, resulting in the development of targeted therapies. Moreover, clinical trials assessing combination therapy with immune checkpoint inhibitors are ongoing and are expected to be efficacious for treating thymic epithelial tumors. We reviewed the current role of systemic chemotherapy, including targeted therapies and immune checkpoint inhibitors, considering recent findings regarding its biology. Abstract Thymic carcinoma is a rare cancer that arises from thymic epithelial cells. Its nature and pathology differ from that of benign thymoma, presenting a poorer prognosis. If surgically resectable, surgery alone or surgery followed by chemoradiotherapy or radiotherapy is recommended by the National Comprehensive Cancer Network Guidelines. Metastatic and refractory thymic carcinomas require systemic pharmacotherapy. Combined carboplatin and paclitaxel, and cisplatin and anthracycline-based regimens have been shown a fair response rate and survival to provide a de facto standard of care when compared with other drugs employed as first-line chemotherapy. Cytotoxic agents have been pivotal for treating thymic carcinoma, as little is known regarding its tumorigenesis. In addition, genetic alterations, including driver mutations, which play an important role in treatments, have not yet been discovered. However, molecular pathways and biomarker studies assessing thymic epithelial tumors have been reported recently, resulting in the development of new agents, such as molecular targeted agents and immune checkpoint inhibitors. As treatment options are currently limited and the prognosis remains poor in metastases and recurrent thymic carcinoma, genetic alterations need to be assessed. In the present review, we focused on the current role of targeted therapies and immune checkpoint inhibitors in treating thymic carcinoma.
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13
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Subbiah S, Nam A, Garg N, Behal A, Kulkarni P, Salgia R. Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research. J Clin Med 2020; 9:jcm9082433. [PMID: 32751469 PMCID: PMC7464169 DOI: 10.3390/jcm9082433] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 12/23/2022] Open
Abstract
Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.
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14
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Wakuda K. Treatment strategy for patients with relapsed small-cell lung cancer: past, present and future. Transl Lung Cancer Res 2020; 9:172-179. [PMID: 32420056 PMCID: PMC7225150 DOI: 10.21037/tlcr.2020.03.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Kazushige Wakuda
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan
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15
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Lohinai Z, Megyesfalvi Z, Dome B, Weiss GJ. Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC). Transl Oncol 2019; 12:1539-1548. [PMID: 31476386 PMCID: PMC6727016 DOI: 10.1016/j.tranon.2019.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/31/2019] [Accepted: 08/02/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND: Molecular underpinnings that may prognosticate survival could increase understanding of small cell lung cancer (SCLC) tumor behavior. Here, we report the clinicopathological characteristics and biomarker profiles of short-term (ST) versus long-term (LT) survival in patients with metastatic SCLC. METHODS: Of the 876 consecutive metastatic SCLC patients receiving standard of care therapy, 44 met the definition of LT and 91 for ST, respectively. Available FFPE tumor tissue blocks were analyzed by next-generation sequencing (NGS). Analysis included gene mutations, copy number variations, mRNA expression, and protein expression by immunohistochemistry, followed by correlation with clinicopathological characteristics. RESULTS: There were no statistically significant and clinically relevant differences in cases with or without FFPE according to major clinicopathological variables in ST and LT. However, according to NGS, five mutually exclusive gene mutations were identified (E1A binding protein P300 [EP300] p.N217S; p.E152K; human epidermal growth factor receptor 4 [ERBB4] p.E317K; BRCA1, DNA repair associated [BRCA1] p.E1661N, and epidermal growth factor receptor [EGFR] p.V742A). Comparing LT vs. ST survivals, a twofold increase was found in the average predicted number of drugs per patient off compendium. We found high SSTR2 mRNA expressions in all LT patients (vs. two [20%] ST patients), which may reflect more benign neuroendocrine tumor characteristics. CONCLUSIONS: Consolidation radiation therapy and higher predicted drug sensitivity for off compendium were associated with LT compared to ST patients in SCLC. NGS profiling of extreme survivals may improve classification of SCLC and possibly identify clinically relevant new targets.
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Affiliation(s)
- Zoltan Lohinai
- National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria.
| | - Zsolt Megyesfalvi
- National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
| | - Balazs Dome
- National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria.
| | - Glen J Weiss
- MiRanostics Consulting, Oro Valley, AZ, United States
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16
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Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA. Current Diagnosis and Management of Small-Cell Lung Cancer. Mayo Clin Proc 2019; 94:1599-1622. [PMID: 31378235 DOI: 10.1016/j.mayocp.2019.01.034] [Citation(s) in RCA: 192] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 01/05/2019] [Accepted: 01/31/2019] [Indexed: 12/25/2022]
Abstract
Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non-small-cell lung cancer. SCLC has high metastatic potential, resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody-drug conjugates are being evaluated in SCLC, with a number of them showing early promise.
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Affiliation(s)
- Shuhang Wang
- Peking University Cancer Hospital, Beijing, China
| | - Stefan Zimmermann
- Département d'Oncologie, service d'Immuno-Oncologie, CHUV, Lausanne, Switzerland
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17
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Abstract
Small cell lung carcinoma (SCLC), also known as high-grade neuroendocrine tumor of the lung, is exceedingly rare in the pediatric population. SCLC is usually fast growing and often has metastasized at diagnosis. It frequently responds well to therapy initially, however, has a high relapse and mortality rate. There are limited published data on SCLC in children and no existing pediatric treatment protocols. In this report, we present a case of extensive stage SCLC in a 15-year-old boy who responded to single-agent gemcitabine therapy and review similar cases reported in the medical literature.
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18
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Abstract
Despite high response rates to initial therapy, relapses are common in patients with small-cell lung cancer (SCLC). Systemic therapy after first-line failure remains important in the treatment paradigm of SCLC. Reinitiation of a previously administered first-line chemotherapy regimen is recommended for relapse > 6 months from completion of initial therapy. For relapse ≤ 6 months of initial therapy, sequential therapy with single agents is recommended. Clinical trial enrollment should be considered at all stages of treatment of SCLC. This review highlights the available treatment options in relapsed SCLC. In particular, we focus on prospective clinical trials demonstrating activity for the most commonly used agents in this setting. We end with a discussion on future directions and emerging targets with potential to improve outcomes in relapsed SCLC.
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Affiliation(s)
- Jun Gong
- City of Hope National Medical Center, Duarte, CA
| | - Ravi Salgia
- City of Hope National Medical Center, Duarte, CA
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19
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Farago AF, Keane FK. Current standards for clinical management of small cell lung cancer. Transl Lung Cancer Res 2018; 7:69-79. [PMID: 29535913 PMCID: PMC5835595 DOI: 10.21037/tlcr.2018.01.16] [Citation(s) in RCA: 179] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/26/2018] [Indexed: 12/11/2022]
Abstract
Small cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma. Despite over 30 years of clinical research, little progress has been made in the management of SCLC, and outcomes remain poor. Here, we review the current clinical standards for management of SCLC and the data supporting these strategies.
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Affiliation(s)
- Anna F. Farago
- Cancer Center, Massachusetts General Hospital, Boston, MA, USA
| | - Florence K. Keane
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
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20
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Zhou K, Wen F, Zhang P, Zhou J, Zheng H, Sun L, Li Q. Cost-effectiveness analysis of sensitive relapsed small-cell lung cancer based on JCOG0605 trial. Clin Transl Oncol 2017; 20:768-774. [DOI: 10.1007/s12094-017-1787-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2017] [Accepted: 10/20/2017] [Indexed: 11/24/2022]
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21
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Pan Y, Kong FW, Wang H, Wang X, Zhang H, Wu WB, Zhang M. A recurrence-free survivor with chemotherapy-refractory small cell lung cancer after pneumonectomy: A case report and review of the literature. Medicine (Baltimore) 2017; 96:e8922. [PMID: 29382030 PMCID: PMC5709029 DOI: 10.1097/md.0000000000008922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
RATIONALE The optimal therapeutic regimen for chemotherapy-refractory and node-positive small-cell lung cancer (SCLC) is criticizable for the lack of evidence. PATIENT CONCERNS A patient with locally advanced SCLC was insensitive to the first-line chemotherapy of etoposide, irinotecan, and cisplatin. DIAGNOSES The patient was diagnosed as SCLC with mediastinal lymph node metastasis by pathological staining. INTERVENTIONS Salvage pneumonectomy and systematic lymph node dissection combined with oral apatinib and mediastinal radiotherapy were performed for him. OUTCOMES The patient survived for more than 2 years without recurrence after the operation and adjuvant therapy. LESSONS For patients with chemotherapy-resistant but resectable SCLC, a timely resection combined with postoperative radiotherapy and apatinib might be effective.
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Affiliation(s)
- Yong Pan
- Department of General Surgery, Xuzhou Infectious Disease Hospital, Xuzhou, China
| | - Feng-Wei Kong
- Department of General Surgery, Xuzhou Infectious Disease Hospital, Xuzhou, China
| | | | - Xiang Wang
- Department of Oncology, Xuzhou Central Hospital Affiliated to Southeast University, Xuzhou, China
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22
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Kim SH, Kim MJ, Kim YJ, Chang H, Kim JW, Lee JO, Lee KW, Kim JH, Bang SM, Lee JS. Paclitaxel as third-line chemotherapy for small cell lung cancer failing both etoposide- and camptothecin-based chemotherapy. Medicine (Baltimore) 2017; 96:e8176. [PMID: 29049199 PMCID: PMC5662365 DOI: 10.1097/md.0000000000008176] [Citation(s) in RCA: 8] [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: 11/26/2022] Open
Abstract
Paclitaxel has been shown to have clinical activity in the treatment of small cell lung cancer (SCLC). However, its role as third-line chemotherapy for SCLC after both etoposide- and camptothecin-based regimens has not been clarified.All patients with refractory SCLC who were treated with paclitaxel-based regimen as third-line chemotherapy between 2005 and 2011 in Seoul National University Bundang Hospital were reviewed retrospectively. Forty patients previously treated with both etoposide- and camptothecin-based chemotherapy were included.The median age of the enrolled patients was 67 years (range, 35-86 years). Most patients (77.5%) received cisplatin plus etoposide as first-line therapy, and camptothecins such as irinotecan or topotecan as second-line therapy. Of 34 patients with measurable lesions, 8 patients (23.5%) achieved partial response and 9 (26.5%) had stable disease. The median progression-free survival (PFS) and overall survival (OS) were 2.5 and 5.9 months, respectively. Predictive factors for OS were performance status (PS) (PS <2 vs ≥2; P = .001), the presence of liver metastasis (P < .001), and number of metastatic sites (<3 vs ≥3; P = .047) in univariate analysis. PS and liver metastasis also remained statistically significant in multivariate analysis. Grade 3 or 4 hematologic toxicity was 20% for neutropenia, and 10% for thrombocytopenia. Other common non-hematological toxicities were peripheral neuropathy and mild liver enzyme elevation.Paclitaxel-based chemotherapy showed modest activity in SCLC patients refractory to both etoposide- and camptothecin-based chemotherapy. PS and presence of liver metastasis were predictive of survival after paclitaxel chemotherapy.
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Affiliation(s)
- Se Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Mi-Jung Kim
- Hematology and Medical Oncology, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Republic of Korea
| | - Yu Jung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Hyun Chang
- Hematology and Medical Oncology, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Republic of Korea
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Jeong-Ok Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Soo-Mee Bang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Jong Seok Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
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23
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Baize N, Monnet I, Greillier L, Quere G, Kerjouan M, Janicot H, Vergnenegre A, Auliac JB, Chouaid C. Second-line treatments of small-cell lung cancers. Expert Rev Anticancer Ther 2017; 17:1033-1043. [DOI: 10.1080/14737140.2017.1372198] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Nathalie Baize
- UTTIOM (Unité Transversale de Thérapeutiques Innovantes en Oncologie Médicale), CHU Angers, France
| | - Isabelle Monnet
- Department of Pulmonology, Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | - Laurent Greillier
- Service d’Oncologie Multidisciplinaire et Innovations Thérapeutiques, AP-HM, Aix-Marseille Université, Marseille, France
| | - Gilles Quere
- Respiratory Disease Department, Brest University Brest, Brest, France
| | - Mallorie Kerjouan
- Respiratory Disease Department, Pontchaillou University Hospital, Rennes, France
| | - Henri Janicot
- Service de pneumologie, CHU Clermont-Ferrand, Clermont Ferrand, France
| | - Alain Vergnenegre
- UOTC (Unité d’Oncologie Thoracique et Cutanée), CHU Limoges, Limoges, France
| | | | - Christos Chouaid
- Department of Pulmonology, Centre Hospitalier Intercommunal de Créteil, Créteil, France
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Abstract
Small cell lung cancer (SCLC) is an aggressive tumor characterized by rapid doubling time and high propensity for early development of disseminated disease. Although most patients respond to initial therapy with a platinum doublet, the majority of those with limited stage and virtually all patients with metastatic disease eventually develop tumor progression for which there are limited treatment options. There have been no recent changes in the treatment of SCLC, with platinum plus etoposide and topotecan as the standard first-line and second-line respectively, neither showing survival benefit over the combination of cyclophosphamide, doxorubicin and vincristine, which was developed in the 1970s. More recently, a new understanding of the biology of SCLC has led to the development of novel drugs, of which the most promising are the immune checkpoint inhibitors and the antibody drug conjugate rovalpituzumab tesirine.
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25
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Okuma Y, Hosomi Y, Miyamoto S, Shibuya M, Okamura T, Hishima T. Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma. BMC Cancer 2016; 16:156. [PMID: 26915359 PMCID: PMC4766615 DOI: 10.1186/s12885-016-2159-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 02/10/2016] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis. METHODS We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort. RESULTS A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4-67.4) and the disease control rate was 85.7 % (60.0-96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6-12.2 months), and median overall survival was 30.0 months (range, 6.2-41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed. CONCLUSIONS S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.
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Affiliation(s)
- Yusuke Okuma
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan.
- Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato, Tokyo, Japan.
| | - Yukio Hosomi
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan.
| | - Shingo Miyamoto
- Department of Clinical Oncology, Japan Red Cross Medical Center, Shibuya, Tokyo, Japan.
| | - Masahiko Shibuya
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan.
| | - Tatsuru Okamura
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan.
| | - Tsunekazu Hishima
- Department of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan.
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Yun T, Kim HT, Han JY, Yoon SJ, Kim HY, Nam BH, Lee JS. A Phase II Study of Weekly Paclitaxel Plus Gemcitabine as a Second-Line Therapy in Patients with Metastatic or Recurrent Small Cell Lung Cancer. Cancer Res Treat 2015; 48:465-72. [PMID: 26044164 PMCID: PMC4843756 DOI: 10.4143/crt.2015.061] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Accepted: 04/14/2015] [Indexed: 11/21/2022] Open
Abstract
Purpose Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen. Materials and Methods Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m2) and G (1,000 mg/m2) on days 1 and 8 of each cycle of 21 days until disease progression. Results Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia. Conclusion Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy.
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Affiliation(s)
- Tak Yun
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Heung Tae Kim
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Ji-Youn Han
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sung Jin Yoon
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Hyae Young Kim
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Byung-Ho Nam
- Cancer Biostatistics Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Jin Soo Lee
- Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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Gervais R, Le Caer H, Monnet I, Falchero L, Baize N, Olivero G, Thomas P, Berard H, Auliac JB, Chouaid C. Second-Line Oral Chemotherapy (Lomustine, Cyclophosphamide, Etoposide) Versus Intravenous Therapy (Cyclophosphamide, Doxorubicin, and Vincristine) in Patients With Relapsed Small Cell Lung Cancer: A Randomized Phase II Study of GFPC 0501. Clin Lung Cancer 2015; 16:100-5. [DOI: 10.1016/j.cllc.2014.10.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 10/19/2014] [Accepted: 10/21/2014] [Indexed: 10/24/2022]
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Response to cytotoxic chemotherapy in patients previously treated with palliative-intent chemotherapy for advanced thymic carcinoma. Clin Lung Cancer 2014; 16:221-7. [PMID: 25468802 DOI: 10.1016/j.cllc.2014.10.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/23/2014] [Accepted: 10/28/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. PATIENTS AND METHODS We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. CONCLUSION Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.
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Allen JW, Moon J, Redman M, Gadgeel SM, Kelly K, Mack PC, Saba HM, Mohamed MK, Jahanzeb M, Gandara DR. Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer. J Clin Oncol 2014; 32:2463-70. [PMID: 25002722 PMCID: PMC4121504 DOI: 10.1200/jco.2013.51.4109] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting. PATIENTS AND METHODS Patients with previously treated SCLC (one line of platinum-based chemotherapy), performance status of 0 to 1, adequate organ function, treated brain metastases, and no recent vascular events or bleeding diatheses were eligible. Eligible patients were stratified as platinum-sensitive or platinum-refractory and randomly assigned to receive weekly topotecan 4 mg/m(2) intravenously (IV) with or without ziv-aflibercept 6 mg/kg IV every 21 days. Progression-free survival (PFS) at 3 months was the primary end point. RESULTS In 189 randomly assigned patients, treatment arms were well balanced with regard to clinical characteristics. The 3-month PFS was significantly improved with the addition of ziv-aflibercept in patients who had platinum-refractory disease (27% v 10%; P = .02) but not in patients with platinum-sensitive disease (24% v 15%; P = .22). Although response rate was low, disease control rate was higher with combination therapy than with topotecan alone in patients who had platinum-sensitive disease (37% v 18%; P = .05) and in those who had platinum-refractory disease (25% v 15%; P = .14). Overall survival (OS) was not significantly improved in either strata. Grades 3 to 5 toxicities were more common with the addition of ziv-aflibercept. CONCLUSION Ziv-aflibercept improved the 3-month PFS in patients who had platinum-refractory SCLC, but its addition increased toxicity. OS was similar with combined ziv-aflibercept and topotecan compared with topotecan in both strata.
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Affiliation(s)
- Jeffrey W Allen
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
| | - James Moon
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Mary Redman
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Shirish M Gadgeel
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Karen Kelly
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Philip C Mack
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Hanna M Saba
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Mohamed K Mohamed
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - Mohammad Jahanzeb
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
| | - David R Gandara
- Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL
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Han JY, Lee YS, Kim BC, Lee GK, Lee S, Kim EH, Kim HM, Bhak J. Whole-genome analysis of a patient with early-stage small-cell lung cancer. THE PHARMACOGENOMICS JOURNAL 2014; 14:503-8. [DOI: 10.1038/tpj.2014.17] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/27/2014] [Accepted: 02/26/2014] [Indexed: 12/31/2022]
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Chan BA, Coward JIG. Chemotherapy advances in small-cell lung cancer. J Thorac Dis 2013; 5 Suppl 5:S565-78. [PMID: 24163749 PMCID: PMC3804877 DOI: 10.3978/j.issn.2072-1439.2013.07.43] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 07/30/2013] [Indexed: 12/26/2022]
Abstract
Although chemotherapeutic advances have recently been heralded in lung adenocarcinomas, such success with small-cell lung cancer (SCLC) has been ominously absent. Indeed, the dismal outlook of this disease is exemplified by the failure of any significant advances in first line therapy since the introduction of the current standard platinum-etoposide doublet over 30 years ago. Moreover, such sluggish progress is compounded by the dearth of FDA-approved agents for patients with relapsed disease. However, over the past decade, novel formulations of drug classes commonly used in SCLC (e.g. topoisomerase inhibitors, anthracyclines, alkylating and platinum agents) are emerging as potential alternatives that could effectively add to the armamentarium of agents currently at our disposal. This review is introduced with an overview on the historical development of chemotherapeutic regimens used in this disease and followed by the recent encouraging advances witnessed in clinical trials with drugs such as amrubicin and belotecan which are forging new horizons for future treatment algorithms.
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Affiliation(s)
- Bryan A. Chan
- Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia
- School of Medicine, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
| | - Jermaine I. G. Coward
- Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia
- School of Medicine, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
- Inflammation & Cancer Therapeutics Group, Mater Research, Level 4, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia
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Yu S, Wang Y, Hu X, Wang H, Hao X, Xu J, Li J, Zhang X, Shi Y. [A retrospective study of the efficacy and toxicity of irinotecan in combination with nedaplatin versus irinotecan in combination with cisplatin as salvage
treatment in refractory or relapsed small cell lung cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2013; 16:470-5. [PMID: 24034994 PMCID: PMC6000632 DOI: 10.3779/j.issn.1009-3419.2013.09.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
背景与目的 对初治进展或复发的小细胞肺癌，目前尚无标准的二线方案，本研究旨在比较伊立替康联合奈达铂或联合顺铂治疗敏感复发或难治性小细胞肺癌的疗效和安全性。 方法 回顾了中国医学科学院肿瘤医院2009年4月-2012年4月诊治的1, 140例小细胞肺癌患者，筛选二线接受伊立替康联合奈达铂（IN）或伊立替康联合顺铂（IC）方案化疗的患者进行分析。 结果 入组的54例患者中，中位无进展生存时间（progression free survival, PFS）为4.9个月，中位总生存时间（overall survival, OS）为13.3个月，IC组的PFS为4.3个月，IN组的PFS为5.4个月（P=0.465）。两组OS分别为13.3个月和14.3个月（P=0.704）。对生存时间的Cox多因素分析显示：二线治疗前的PS评分（P=0.003）、二线治疗前的转移部位个数（P=0.023）、接受化疗的周期数（P=0.003）是独立预后因素。整体的不良反应可耐受，IN组血液学毒性较重，IC组腹泻发生率较高，但均无统计学意义。 结论 伊立替康联合铂类是对于敏感复发和难治性小细胞肺癌有效且耐受性好的方案，伊立替康联合奈达铂在疗效及安全性方面都不劣于其联合顺铂。
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Affiliation(s)
- Shufei Yu
- Department of Medical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing 100021, China
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Kalemkerian GP, Akerley W, Bogner P, Borghaei H, Chow LQ, Downey RJ, Gandhi L, Ganti AKP, Govindan R, Grecula JC, Hayman J, Heist RS, Horn L, Jahan T, Koczywas M, Loo BW, Merritt RE, Moran CA, Niell HB, O'Malley J, Patel JD, Ready N, Rudin CM, Williams CC, Gregory K, Hughes M. Small cell lung cancer. J Natl Compr Canc Netw 2013; 11:78-98. [PMID: 23307984 DOI: 10.6004/jnccn.2013.0011] [Citation(s) in RCA: 292] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.
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Smith J, Reidy-Lagunes D. The Management of Extrapulmonary Poorly Differentiated (High-Grade) Neuroendocrine Carcinomas. Semin Oncol 2013; 40:100-8. [DOI: 10.1053/j.seminoncol.2012.11.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Nakayama Y, Higure A, Shibao K, Sato N, Matayoshi N, Yamaguchi K. Synchronous occurrence of early neuroendocrine carcinoma and tubular adenocarcinoma in the stomach. Clin J Gastroenterol 2012; 5:307-311. [PMID: 26182399 DOI: 10.1007/s12328-012-0320-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Accepted: 06/27/2012] [Indexed: 12/29/2022]
Abstract
This report describes a patient with early neuroendocrine carcinoma (NEC) and tubular adenocarcinoma in the stomach. A 74-year-old Japanese male experienced epigastralgia. Endoscopic examination revealed two small lesions; one was an elevated lesion with ulceration at the posterior wall of the pre-pylorus and the other was a depressed lesion at the greater curvature of the antrum. Pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the pre-pylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach. A distal partial gastrectomy with lymph node dissection was performed. A histopathological examination revealed NEC at the lesion on the pre-pylorus and well differentiated tubular adenocarcinoma at the lesion on the antrum. These two lesions were completely separate from each other. Therefore, this case is thought to demonstrate the synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
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Affiliation(s)
- Yoshifumi Nakayama
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan.
- Department of Gastroenterological and General Surgery, Wakamatsu Hospital of University of Occupational and Environmental Health, 1-17-1 Hamamachi, Wakamatsu-ku, Kitakyushu, 808-0024, Japan.
| | - Aiichirou Higure
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan
| | - Kazunori Shibao
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan
| | - Nagahiro Sato
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan
- Department of Gastroenterological and General Surgery, Wakamatsu Hospital of University of Occupational and Environmental Health, 1-17-1 Hamamachi, Wakamatsu-ku, Kitakyushu, 808-0024, Japan
| | - Nobutaka Matayoshi
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan
| | - Koji Yamaguchi
- Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan
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Califano R, Abidin AZ, Peck R, Faivre-Finn C, Lorigan P. Management of small cell lung cancer: recent developments for optimal care. Drugs 2012; 72:471-90. [PMID: 22356287 DOI: 10.2165/11597640-000000000-00000] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Small cell lung cancer (SCLC) represents approximately 13% of all lung cancer diagnoses and the incidence has reduced over the last 20 years. Treatment of SCLC remains challenging because of its rapid growth, early dissemination and development of drug resistance during the course of the disease. Chemotherapy remains the cornerstone of treatment for limited (LD) and extensive disease (ED), with concurrent chemotherapy and radical thoracic radiotherapy representing the best treatment option for fit patients with LD. Platinum-based chemotherapy is the treatment of choice in fit patients with good organ function, and the radiosensitizing effect of cisplatin is critically important for concurrent chemoradiotherapy in LD. Anthracycline-containing regimens represent a viable alternative for patients where platinum-based chemotherapy is contraindicated. Patients who relapse or progress after first-line chemotherapy have a very poor prognosis. Second-line therapy may produce a modest clinical benefit. Maintenance chemotherapy has not been shown to convincingly improve outcomes for SCLC. A number of targeted agents have been investigated in LD and ED, mostly in unselected populations, with disappointing results. Prophylactic cranial irradiation has been shown to reduce the incidence of brain metastases and prolong survival for both LD and ED without negative impact on quality of life (QOL) and cognitive function. Ongoing trials will shed some light on the impact of thoracic radiotherapy on QOL, symptom control and survival in ED SCLC patients who benefitted from first-line chemotherapy.
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Affiliation(s)
- Raffaele Califano
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
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Karim SM, Zekri J. Chemotherapy for small cell lung cancer: a comprehensive review. Oncol Rev 2012; 6:e4. [PMID: 25992206 PMCID: PMC4419639 DOI: 10.4081/oncol.2012.e4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2011] [Revised: 03/18/2012] [Accepted: 03/27/2012] [Indexed: 01/10/2023] Open
Abstract
Combination chemotherapy is the current strategy of choice for treatment of small cell lung cancer (SCLC). Platinum containing combination regimens are superior to non-platinum regimens in limited stage-SCLC and possibly also in extensive stage-SCLC as first and second-line treatments. The addition of ifosfamide to platinum containing regimens may improve the outcome but at the price of increased toxicity. Suboptimal doses of chemotherapy result in inferior survival. Early intensified, accelerated and high-dose chemotherapy gave conflicting results and is not considered a standard option outside of clinical trials. A number of newer agents have provided promising results when used in combination regimens, for example, gemcitabine, irinotecan and topotecan. However, more studies are required to appropriately evaluate them. There is a definitive role for radiotherapy in LD-SCLC. However, timing and schedule are subject to further research. Novel approaches are currently being investigated in the hope of improving outcome.
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Affiliation(s)
| | - Jamal Zekri
- King Faisal Specialist Hospital and Research Center, Saudi Arabia
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Abstract
Confined to one side of the chest, limited stage small cell lung cancer is treated with a combination of chemotherapy and radiotherapy, yet has a long-term survival rate of only 15%. Extensive stage disease has initial response rates to chemotherapy exceeding 70%. However, the disease almost invariably progresses and becomes fatal. Many recent clinical trials have failed to show superiority of newer chemotherapeutics or targeted therapies compared with the standard chemotherapy backbone of platinum plus etoposide. Numerous promising targeted therapies and other agents are still in development.
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Abstract
Small-cell lung cancer (SCLC) recurs in the majority of patients, even though most patients respond to first-line therapy. Therefore second-line therapy is considered in almost all patients with SCLC in the course of disease. Efficacy of second-line chemotherapy is much lower than that of first-line treatment, but it can provide significant palliation and prolongation of survival for many patients. Patients receiving second-line therapy are divided into relapsed and refractory patients. Relapsed disease is defined as relapse or progression at least 3 months after the end of first-line therapy. All other situations, including a treatment-free interval <3 months or no response to first-line therapy, are termed refractory disease. The benefit from second-line chemotherapy is highest in patients with relapsed disease. Topotecan monotherapy improves survival and quality of life, as well as cancer-related symptoms in the second-line setting. Alternatively, doxorubicin-based combination therapy can be administered with a similar outcome but a slightly lower rate of symptom control. In refractory patients no standard therapy exists. Amrubicin, a novel anthracyline, showed promising activity in refractory and relapsed patients. Phase III trials are ongoing. Other agents with activity include irinotecan, paclitaxel, docetaxel, gemcitabine, bendamustine and vinorelbine.
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Affiliation(s)
- Alexander Schmittel
- Aerzteforum Seestrasse, Medizinisches Versorgungszentrum, Hematology, Oncology, Infectious Diseases, Seestrasse 64, 13347 Berlin, Germany.
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William WN, Glisson BS. Novel strategies for the treatment of small-cell lung carcinoma. Nat Rev Clin Oncol 2011; 8:611-9. [PMID: 21691321 DOI: 10.1038/nrclinonc.2011.90] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Small-cell lung cancer (SCLC) is a disease with a poor prognosis and limited treatment options. Over the past 30 years, basic and clinical research have translated to little innovation in the treatment of this disease. The Study of Picoplatin Efficacy After Relapse (SPEAR) evaluated best supportive care with or without picoplatin for second-line SCLC treatment and failed to meet its primary end point of overall survival. As the largest second-line, randomized study in patients with SCLC, SPEAR provides an opportunity to critically examine the drug development model in this disease. In this Review, we discuss the current standard approach for the management of SCLC that progresses after first-line therapy, analyze the preliminary data that supported the evaluation of picoplatin in this setting, and critically evaluate the SPEAR trial design and results. Lastly, we present advances in the understanding of the molecular biology of SCLC that could potentially inform future clinical trials and hopefully lead to the successful development of molecular targeted agents for the treatment of this disease.
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Affiliation(s)
- William N William
- Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030, USA
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Hata A, Katakami N, Fujita S, Kaji R, Nanjo S, Otsuka K, Kida Y, Higashi Y, Tachikawa R, Hayashi M, Nishimura T, Tomii K. Amrubicin at a lower-dose with routine prophylactic use of granulocyte-colony stimulating factor for relapsed small-cell lung cancer. Lung Cancer 2011; 72:224-8. [DOI: 10.1016/j.lungcan.2010.08.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2010] [Revised: 08/03/2010] [Accepted: 08/09/2010] [Indexed: 12/01/2022]
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Haddadin S, Perry MC. History of Small-Cell Lung Cancer. Clin Lung Cancer 2011; 12:87-93. [DOI: 10.1016/j.cllc.2011.03.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2010] [Revised: 07/12/2010] [Accepted: 07/16/2010] [Indexed: 01/22/2023]
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Phase II study of the histone deacetylase inhibitor Romidepsin in relapsed small cell lung cancer (Cancer and Leukemia Group B 30304). J Thorac Oncol 2011; 5:1644-8. [PMID: 20871263 DOI: 10.1097/jto.0b013e3181ec1713] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Treatment of small cell lung cancer (SCLC) is initially gratifying with most patients responding to platinum-based chemotherapy. Treatment of relapsed disease gives much lower response rates of short duration. We undertook this study of the protein deacetylase inhibitor Romidepsin in chemosensitive recurrent SCLC based on preclinical data that suggested this to be an active target. METHODS Patients had recurrent chemosensitive SCLC (relapse ≥90 days since completion of platinum-based chemotherapy). Treatment was administered as weekly infusions of Romidepsin at 13 mg/m(2) for 3 of 4 weeks. We designed a two-stage phase II study targeting a response rate of 30% (<10% response would be uninteresting and ≥30% worthy of further study). RESULTS Sixteen patients (10 male, 6 female) were accrued to the first stage of this study. Most (11 patients, 69%) presented with extensive-stage SCLC, and all had received prior chemotherapy, with 11 having received prior radiation. Eastern Cooperative Oncology Group performance status was excellent with 0 in 6 patients (38%) and 1 in 10 patients. No objective responses were seen, and stable disease was the best response seen in 3 patients (19%). Toxicity was modest with 3 patients suffering grade 3 toxicity (lymphopenia, insomnia, nausea, vomiting, and hyponatremia) and one patient with grade 4 thrombocytopenia. Median progression-free survival was 1.8 months, and median overall survival was 6 months. CONCLUSION Romidepsin given on a weekly schedule in patients with chemosensitive, recurrent SCLC was inactive and will not be pursued further in this setting.
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Tarhini A, Kotsakis A, Gooding W, Shuai Y, Petro D, Friedland D, Belani CP, Dacic S, Argiris A. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clin Cancer Res 2010; 16:5900-7. [PMID: 21045083 DOI: 10.1158/1078-0432.ccr-10-0802] [Citation(s) in RCA: 100] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC. EXPERIMENTAL DESIGN Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue. RESULTS A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11-40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97-4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093). CONCLUSIONS Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered.
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Affiliation(s)
- Ahmad Tarhini
- University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
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Nakazuru S, Yoshio T, Suemura S, Itoh M, Araki M, Yoshioka C, Ohta M, Sueyoshi Y, Ohta T, Hasegawa H, Morita K, Toyama T, Kuzushita N, Kodama Y, Mano M, Mita E. Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report. World J Gastroenterol 2010; 16:3853-6. [PMID: 20698050 PMCID: PMC2921099 DOI: 10.3748/wjg.v16.i30.3853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partial tumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.
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Puglisi M, Dolly S, Faria A, Myerson JS, Popat S, O'Brien MER. Treatment options for small cell lung cancer - do we have more choice? Br J Cancer 2010; 102:629-38. [PMID: 20104223 PMCID: PMC2837580 DOI: 10.1038/sj.bjc.6605527] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2009] [Revised: 12/02/2009] [Accepted: 12/08/2009] [Indexed: 01/22/2023] Open
Abstract
Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.
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Affiliation(s)
- M Puglisi
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - S Dolly
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - A Faria
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - J S Myerson
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - S Popat
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - M E R O'Brien
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
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Lebeau B, Chouaïd C, Baud M, Masanès MJ, Febvre M. Oral second- and third-line lomustine–etoposide–cyclophosphamide chemotherapy for small cell lung cancer. Lung Cancer 2010; 67:188-93. [DOI: 10.1016/j.lungcan.2009.03.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2009] [Revised: 03/02/2009] [Accepted: 03/20/2009] [Indexed: 11/25/2022]
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Isobe K, Kobayashi K, Kosaihira S, Kurimoto F, Sakai H, Uchida Y, Nagai Y, Yamaguchi T, Miyanaga A, Ando M, Mori G, Hino M, Gemma A. Phase II study of nimustine hydrochloride (ACNU) plus paclitaxel for refractory small cell lung cancer. Lung Cancer 2009; 66:350-4. [DOI: 10.1016/j.lungcan.2009.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2008] [Revised: 02/25/2009] [Accepted: 03/01/2009] [Indexed: 10/21/2022]
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