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Pat Fong W, Li ZJ, Ren C, Guan WL, Zuo MX, Zhang TQ, Li BK, Zheng Y, Wu XJ, Ding PR, Chen G, Pan ZZ, Yuan YF, Tan Q, Wang ZQ, Li YH, Wang DS. Percutaneous hepatic artery infusion chemotherapy with oxaliplatin and fluoropyrimidines in treatment-resistant colorectal cancer patients with unresectable liver metastases: a retrospective cohort study. HPB (Oxford) 2025; 27:289-298. [PMID: 39668070 DOI: 10.1016/j.hpb.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/19/2024] [Accepted: 11/25/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND Subsequent lines of therapy for chemotherapy-resistant metastatic colorectal cancer (CRC) have shown limited efficacy. Herein, we retrospectively investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin plus 5-FU/FUDR in patients with unresectable colorectal liver metastases (CRLM) who progressed following standard chemotherapy regimens. METHODS From March 2017 to April 2023, CRC patients with unresectable CRLM who progressed following standard chemotherapy and subsequently received HAIC oxaliplatin plus 5-FU/FUDR were evaluated. Objective response rate (ORR), disease control rate (DCR), median depth of tumor response (DpR), no evidence of disease (NED) rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. RESULTS A total of 21 patients who progressed after a median of two (range: 1-4) lines of standard systemic chemotherapy were included. The ORR and DCR were 28.6 % and 95.2 %, respectively, with six patients reaching partial response. Additionally, the median DpR was 10.6 %, and seven patients underwent successful conversion surgery. Stratification revealed significantly better PFS in patients with liver-limited metastases compared to those with concurrent hepatic and extrahepatic metastases (P = 0.0003). CONCLUSION HAIC oxaliplatin plus 5-FU/FUDR is a robust regimen for treatment-resistant CRC patients with unresectable CRLM, particularly those with liver-limited disease.
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Affiliation(s)
- William Pat Fong
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zi-Jing Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Chao Ren
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wen-Long Guan
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Meng-Xuan Zuo
- Department of Minimally Invasive & Interventional Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Tian-Qi Zhang
- Department of Minimally Invasive & Interventional Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bin-Kui Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yun Zheng
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Jun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yun-Fei Yuan
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qiong Tan
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Qiang Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-Hong Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
| | - De-Shen Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Hematol Oncol Clin North Am 2025; 39:1-24. [PMID: 39510667 DOI: 10.1016/j.hoc.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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Connell LC, Kemeny NE. Intraarterial Chemotherapy for Liver Metastases. Hematol Oncol Clin North Am 2025; 39:143-159. [PMID: 39510670 DOI: 10.1016/j.hoc.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.
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Affiliation(s)
- Louise C Connell
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA.
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Walle GT, Kitaw TA, Adane S. Incidence and determinants of mortality among patients with colorectal cancer in oncology centers of Amhara region, Ethiopia, 2024: multicenter retrospective follow up study. BMC Cancer 2025; 25:102. [PMID: 39827340 PMCID: PMC11742809 DOI: 10.1186/s12885-025-13462-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 01/06/2025] [Indexed: 01/22/2025] Open
Abstract
INTRODUCTION Colorectal cancer is a significant cause of mortality globally, with several factors impacting patient outcomes, including access to healthcare, early detection, and treatment. Despite this, the specific factors affecting incidence of death among colorectal cancer patients in the Amhara region have not been thoroughly investigated. Thus, this study seeks to assess incidence and determinants of mortality among colorectal cancer patients in Amhara Region oncology centers. RESULTS The mean age of the participants was 48.6 years (SD ± 15). Median survival time was 23.8 months. The overall incidence rate or incidence density of a colorectal cancer mortality rate was 2.9 per 100 person-months (95% CI: 2.5-3.4). Survival rates of colorectal cancer patients 1and 5 year was 69.78% and 16.1%, respectively. The result of the multivariable analysis showed that colorectal cancer patients who had presenting symptoms [AHR = 2.67 (95% CI: 1.95, 3.67)], Base line HGB level < 12.5 mg/dl [AHR = 1.63 (95% CI: 1.12, 2.37)], WHO or ECOG poor performance status [AHR = 2.99 (95% CI: 2.17, 4.12), late stage of cancer [AHR = 2.32 (95% CI: 1.42, 3.79)] and location of tumor on colorectal [AHR = 1.76 (95% CI: 1.20, 2.55)] were significantly associated with mortality of colorectal cancer. CONCLUSION AND RECOMMENDATION The study highlights significant findings on the survival and mortality of colorectal cancer patients. The overall mortality rate was 2.9 per 100 person-months. Multivariable analysis identified presenting symptoms, low baseline hemoglobin levels, poor performance status, late-stage cancer, and tumor location as significant predictors of mortality. Highlighting the need for early detection and targeted care strategies.
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Affiliation(s)
| | | | - Seteamlak Adane
- School of Public health, College of Health Science, Woldia University, Woldia, Ethiopia
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5
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Valéry M, Tanguy ML, Gelli M, Smolenschi C, Hollebecque A, Boilève A, de Sevilla EF, Tselikas L, Bonnet B, Goéré D, Taïeb J, Boige V, Ducreux M, Malka D. Oxaliplatin-induced peripheral neuropathy with hepatic arterial versus intravenous infusion in metastatic colorectal cancer. Support Care Cancer 2024; 32:660. [PMID: 39283505 DOI: 10.1007/s00520-024-08807-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 08/13/2024] [Indexed: 10/20/2024]
Abstract
BACKGROUND Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. METHODS We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000-05 trials and through a review of Gustave Roussy patients' electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. RESULTS A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). CONCLUSION The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN.
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Affiliation(s)
- Marine Valéry
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Marie-Laure Tanguy
- Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Équipe Labellisée Ligue Contre Le Cancer, Oncostat U1018, INSERM, Université Paris-Saclay, Villejuif, France
| | - Maximiliano Gelli
- Département de Chirurgie Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Cristina Smolenschi
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Département d'Innovation Thérapeutique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Antoine Hollebecque
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Département d'Innovation Thérapeutique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Alice Boilève
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France
| | | | - Lambros Tselikas
- Département d'Imagerie Médicale et de Radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Baptiste Bonnet
- Département d'Imagerie Médicale et de Radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Diane Goéré
- Service de Chirurgie Viscérale, Cancérologique et Endocrinienne, Hôpital Universitaire Saint-Louis, Paris, France
| | - Julien Taïeb
- Service d'Oncologie Digestive, Hôpital Européen Georges Pompidou, Paris, France
| | - Valérie Boige
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Michel Ducreux
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France
| | - David Malka
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France.
- Département d'Oncologie Médicale, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014 Paris, France.
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Meng W, Pan L, Huang L, Li Q, Sun Y. Applications of image-guided locoregional transarterial chemotherapy in patients with inoperable colorectal cancer: a review. Front Oncol 2024; 14:1464242. [PMID: 39246324 PMCID: PMC11377196 DOI: 10.3389/fonc.2024.1464242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 08/08/2024] [Indexed: 09/10/2024] Open
Abstract
With the development of comprehensive treatment, locoregional transarterial chemotherapy has become an alternative conversion therapy, palliative therapy, and neoadjuvant therapy for many solid malignant tumors. Locoregional transarterial chemotherapy, which is most frequently used for treating liver cancer, has the characteristics of high regional efficacy and few systemic adverse reactions. In recent years, the number of relevant reports of locoregional chemotherapy for treating initially inoperable colorectal cancer (CRC), including non-metastatic and metastatic CRC, has gradually increased. However, the specific treatment options for such locoregional therapy are not the same, and its indications, medication regimens and combined treatments have not reached any consensus. In this review, the application status of locoregional transarterial chemotherapy in primary and metastatic CRC patients has been reviewed and summarized to provide a reference for future clinical work and scientific research.
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Affiliation(s)
- Wenjun Meng
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Lu Pan
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Li Huang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Qing Li
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Sun
- Department of Oncology and Hematology, Air Force Hospital of Western Theater Command, Chengdu, China
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Popescu I, Dudău AM, Dima S, Herlea V, Croitoru VM, Dinu IM, Miron M, Lupescu I, Croitoru-Cazacu IM, Dumitru R, Croitoru AE. Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:696. [PMID: 38792879 PMCID: PMC11123219 DOI: 10.3390/medicina60050696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 04/14/2024] [Accepted: 04/19/2024] [Indexed: 05/26/2024]
Abstract
Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.
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Affiliation(s)
- Ionuț Popescu
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
| | - Ana-Maria Dudău
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Simona Dima
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad Herlea
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Pathology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad M. Croitoru
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Mihaela Dinu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Monica Miron
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Lupescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Irina M. Croitoru-Cazacu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
| | - Radu Dumitru
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Adina Emilia Croitoru
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
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Cherchenko K, Lukashenko A, Ostapenko Y, Patsko V, Vinohradova M, Valikhnovska K, Pamanska S. INTRA-ARTERIAL CHEMOTHERAPY AS A CLINICAL OPTION FOR METASTATIC COLORECTAL CANCER: CONVERSION OF INOPERABLE LIVER METASTASES TO OPERABLE ILLUSTRATED WITH A CLINICAL CASE. Exp Oncol 2024; 45:515-522. [PMID: 38328838 DOI: 10.15407/exp-oncology.2023.04.515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Indexed: 02/09/2024]
Abstract
Colorectal cancer exerts a very high level of liver metastases, even on primary diagnosis, with 80%-90% unresectable nodules. At the same time, the possibility of resection has a significant impact on survival: 5-year survival is 6%-10% without liver surgery and up to 30% upon resection of liver metastases. Finding ways to improve resectability is a topical search for doctors all over the world. One of the promising methods to convert unresectable liver metastases of colorectal cancer into resectable ones is a hepatic artery infusion, or intra-arterial chemotherapy allowing for the delivery of cytotoxic drugs directly to the common hepatic artery via catheter or pump with decreased systemic toxicity and increased local drug concentration. In this article, we discuss the literature data on the impact of intra-arterial chemotherapy on the resectability of colorectal metastases in the liver and present the results of the successful clinical case. The literature shows a positive impact of the hepatic artery infusion on the resectability of hepatic metastases of colorectal cancer. The National Cancer Institute (Ukraine) has its own experience in hepatic artery infusion with further resection of primary-unresectable colorectal metastases in the liver. In our clinical case, a patient with liver-limited metastasis of colorectal cancer was initially inoperable due to the size of tumor lesions and an insufficient residual volume of the liver. Hepatic artery infusion tactics was chosen for this patient. The patient received six cycles of intra-arterial chemotherapy, namely five FOLFOX cycles and one 5-FU cycle, and then met the resectability criteria. Also, it is important to notice that the case demonstrates chemoresistance overcoming, since the patient had disease progression before, following systemically administered XELOX, and the period until readmission of the drugs was less than 6 months. So, hepatic artery infusion can be considered a promising method to convert unresectable liver metastases of colorectal cancer into resectable ones for highly selected patients.
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Affiliation(s)
- K Cherchenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - A Lukashenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - Yu Ostapenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - V Patsko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - M Vinohradova
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - K Valikhnovska
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - S Pamanska
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
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9
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Malka D, Verret B, Faron M, Guimbaud R, Caramella C, Edeline J, Galais MP, Bengrine-Lefevre L, Smith D, Dupont-Bierre E, De Baere T, Goéré D, Dartigues P, Lacroix L, Boige V, Gelli M, Pignon JP, Ducreux M. Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial. Eur J Cancer 2023; 195:113400. [PMID: 37922632 DOI: 10.1016/j.ejca.2023.113400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. METHODS In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). RESULTS 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. CONCLUSION HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.
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Affiliation(s)
- David Malka
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Département d'Oncologie Médicale, Institut Mutualiste Montsouris, Paris, France.
| | - Benjamin Verret
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Matthieu Faron
- Service de Biostatistique et Epidémiologie, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France; Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | | | - Caroline Caramella
- Département d'Imagerie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | | | | | | | - Denis Smith
- Centre Hospitalier Universitaire Saint-André, Bordeaux, France
| | | | - Thierry De Baere
- Département d'Imagerie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Diane Goéré
- Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Peggy Dartigues
- Département de Pathologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Ludovic Lacroix
- Département de Biologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Valérie Boige
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Maximiliano Gelli
- Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Jean-Pierre Pignon
- Service de Biostatistique et Epidémiologie, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France
| | - Michel Ducreux
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Centre Hospitalier Universitaire Paul Brousse, Villejuif, France
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10
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Judge SJ, Ghalambor T, Cavnar MJ, Lidsky ME, Merkow RP, Cho M, Dominguez-Rosado I, Karanicolas PJ, Mayo SC, Rocha FG, Fields RC, Patel RA, Kennecke HF, Koerkamp BG, Yopp AC, Petrowsky H, Mahalingam D, Kemeny N, D'Angelica M, Gholami S. Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network. Ann Surg Oncol 2023; 30:7362-7370. [PMID: 37702903 PMCID: PMC11108096 DOI: 10.1245/s10434-023-14207-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 07/06/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.
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Affiliation(s)
- Sean J Judge
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Tara Ghalambor
- Department of Surgery, University of California, Davis, Sacramento, CA, USA
| | - Michael J Cavnar
- Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Ryan P Merkow
- Department of Surgery, Northwestern University, Chicago, IL, USA
| | - May Cho
- Department of Medicine, University of California Irvine, Orange, CA, USA
| | - Ismael Dominguez-Rosado
- Department of Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
| | - Paul J Karanicolas
- Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Skye C Mayo
- Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
| | - Flavio G Rocha
- Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
| | - Ryan C Fields
- Division of Surgical Oncology, Department of Surgery, Alvin J. Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO, USA
| | - Reema A Patel
- Department of Medical Oncology, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Hagen F Kennecke
- GI Oncology, Providence Health Cancer Institute, Portland, OR, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Adam C Yopp
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Henrik Petrowsky
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | | | - Nancy Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sepideh Gholami
- Department of Surgery, Northwell Health Cancer Institute, New Hyde Park, NY, USA.
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11
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Bergamaschi L, Chiaravalli S, Signoroni S, Di Bartolomeo M, Ferrari A. Management and pharmacotherapy of pediatric colorectal carcinoma: a review. Expert Opin Pharmacother 2023; 24:1527-1535. [PMID: 37358925 DOI: 10.1080/14656566.2023.2230123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 06/28/2023]
Abstract
INTRODUCTION Colorectal carcinoma (CRC) is one of the most common tumors in adult, but is extremely rare in children. In childhood, CRC often presents unfavorable aggressive histotypes, advanced clinical stage at onset and a worse prognosis. Pediatric CRC series are limited and include few patients, therefore information about treatment strategy and pharmacotherapy is scarce. For this reason, management of these patients represents a real challenge for pediatric oncologists. AREAS COVERED The authors provide an overview of the general features and management strategies of pediatric CRC with specific attention to systemic treatment. Literature data regarding pharmacotherapy in published pediatric series are summarized and analyzed in detail, according to adult treatment standards. EXPERT OPINION In the absence of specific recommendations for pediatric CRC, the general therapeutic strategy should follow the same principles as for adults and should be the result of a multidisciplinary discussion. Patient access to optimal treatment is difficult due to the lack of new drugs approved for the pediatric age group and non-availability of clinical trials. Collaboration between pediatric and adult oncologists is considered crucial in order to overcome these issues and find solutions to increase knowledge and improve the outcome of such a rare disease in children.
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Affiliation(s)
- Luca Bergamaschi
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Stefano Chiaravalli
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Stefano Signoroni
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Di Bartolomeo
- Gastrointestinal Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Andrea Ferrari
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
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12
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Kim JS, Kim H, Lee SY, Han YD, Han K, Min BS, Kim MD, Won JY, Beom SH, Shin SJ, Kim HS, Han DH, Ahn JB. Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study - (NCT05103020) - study protocol. BMC Cancer 2023; 23:691. [PMID: 37481515 PMCID: PMC10363309 DOI: 10.1186/s12885-023-11085-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 06/16/2023] [Indexed: 07/24/2023] Open
Abstract
BACKGROUND Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.
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Affiliation(s)
- Ji Su Kim
- Division of Hepatobiliary and Pancreas Surgery, Incheon St. Mary's Hospital, The Catholic University College of Medicine, Incheon, Korea
| | - Hyunwook Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Seo Young Lee
- Department of Medical Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Dae Han
- Department of Colorectal Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kichang Han
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Soh Min
- Department of Colorectal Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Yun Won
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Hoon Beom
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Sang Joon Shin
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Han Sang Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
- Graduate School of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
| | - Dai Hoon Han
- Department of Hepatobiliary and Pancreatic Surgery, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
| | - Joong Bae Ahn
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
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13
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Ouyang H, Ma W, Si T, Liu D, Chen P, Gerdtsson AS, Song J, Ni Y, Luo J, Yan Z. Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis. Clin Colorectal Cancer 2023; 22:111-119. [PMID: 36473779 DOI: 10.1016/j.clcc.2022.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND The significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM. PATIENT AND METHODS The PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed. RESULTS The main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor. CONCLUSION Our findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.
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Affiliation(s)
- Huaqiang Ouyang
- Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Weidong Ma
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Pancreatic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tongguo Si
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Donglin Liu
- Department of Mathematics, Lund University, Lund, Sweden
| | - Ping Chen
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Anna Sandström Gerdtsson
- Department of Immunotechnology, CREATE Health Translational Cancer Center, Lund University, Lund, Sweden
| | - Jiahong Song
- Department of Cardiology, The second hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Yue Ni
- The Nursing Department, Beijing Bo Ai Hospital, China Rehabilitation Research Center, Beijing, China
| | - Juanjuan Luo
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Zhuchen Yan
- Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
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14
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Cervantes A, Adam R, Roselló S, Arnold D, Normanno N, Taïeb J, Seligmann J, De Baere T, Osterlund P, Yoshino T, Martinelli E. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34:10-32. [PMID: 36307056 DOI: 10.1016/j.annonc.2022.10.003] [Citation(s) in RCA: 748] [Impact Index Per Article: 374.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/06/2022] [Accepted: 10/06/2022] [Indexed: 02/08/2023] Open
Affiliation(s)
- A Cervantes
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - R Adam
- AP-HP Hôpital Paul Brousse, Université Paris-Saclay, ER "Chronothérapie, Cancers, Transplantation", Villejuif, France
| | - S Roselló
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - D Arnold
- Department of Oncology and Hematology, Asklepios Tumourzentrum Hamburg, AK Altona, Hamburg, Germany
| | - N Normanno
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumouri, 'Fondazione G. Pascale'-IRCCS, Naples, Italy
| | - J Taïeb
- Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Assitance Publique-Hôpitaux de Paris AP-HP Paris Centre, Paris, France; Paris Cancer Institute SIRIC CARPEM, Centre de Recherche des Cordeliers, Université Paris-Cité, Paris, France
| | - J Seligmann
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - T De Baere
- Department of Interventional Radiology, Gustave Roussy, Villejuif, France; University of Paris-Saclay, UFR Médecine Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, France; Centre d'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France
| | - P Osterlund
- Tampere University Hospitals and University, Tampere, Finland; Tema Cancer/GI-oncology, Karolinska Comprehensive Cancer Centre, Karolinska Institute, Solna, Sweden
| | - T Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - E Martinelli
- Department of Precision Medicine, Oncology Unit, Università della Campania "L. Vanvitelli", Naples, Italy
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15
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Rigault E, Lacas B, Glehen O, Smith D, Dupont-Bierre E, Guimbaud R, Malka D, Boige V, Fuerea A, Pignon JP, Ducreux M. Intra-arterial hepatic bevacizumab and systemic chemotherapy in hepatic metastasis of colorectal cancer: A phase II multicentric trial in second-line treatment. Cancer Treat Res Commun 2023; 34:100674. [PMID: 36565566 DOI: 10.1016/j.ctarc.2022.100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/07/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Intra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to assess the efficacy and safety of IAH bevacizumab combined to systemic chemotherapy after first-line treatment failure in patients with CRLM. METHODS Included patients had dominant or isolated unresectable CRLM progressing after standard first-line treatment for metastases of colorectal cancer. Three patients had less than 30% liver invasion, three patients between 30 and 50%, two more than 50% and data was missing in two patients. An intra-hepatic catheter was implanted surgically or percutaneously. Bevacizumab 7.5 mg/kg was administered once every 3 weeks in combination with capecitabine 2000 mg/m² per day for 2 weeks and oxaliplatin 130 mg/m² or irinotecan 200 mg/m² once every 3 weeks. The primary end-point was the objective response rate. RESULTS Between June 2013 and February 2015, 10 patients were included. The trial was prematurely closed because of the lack of financial support and poor accrual. The patients had a median of 6 [1-9] cycles of treatment. Partial response was achieved in 2 patients (20%) and a R0 liver metastases resection in one another. All patients died of disease progression. The median overall and progression-free survival rates were respectively 14.0 (95% IC [4.8 - 25.8] and 5.4 months (95% IC [1.6 - 6.2]). Four patients had severe side effects but no toxic death occurred. CONCLUSION IAH bevacizumab combined to systemic chemotherapy is feasible and safe in patients with unresectable isolated or dominant CRLM progressing after a first-line systemic treatment. Based on the low number of patients included in our study, our results suggest that this treatment does not increase dramatically the response rate versus an adapted systemic treatment. However, considering the safety data provided in this study, arterial infusion of bevacizumab in adjunction to chemotherapeutic agents could be evaluated in the future.
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Affiliation(s)
- Eugénie Rigault
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Benjamin Lacas
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Center, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Gustave Roussy, Villejuif, France
| | - Olivier Glehen
- Département de Chirurgie Digestive, Hospices Civils de Lyon, Université Lyon Rhône, France
| | - Denis Smith
- Département d'Hépato-Gastro-Enterologie et d'oncologie digestive, Hôpital Haut-Lévêque, Bordeaux, France
| | | | - Rosine Guimbaud
- Département d'oncologie médicale, Université de Toulouse, Toulouse, France
| | - David Malka
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France; Unité Dynamique des Cellules Tumorales - Inserm U1279, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Valérie Boige
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Alina Fuerea
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Jean-Pierre Pignon
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Center, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France; Unité Dynamique des Cellules Tumorales - Inserm U1279, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Université Paris-Saclay, Saint Aubin, France.
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16
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Randrian V, Pernot S, Sionneau B, Smith D, Lim A, Touchefeu Y, Gallois C, Turpin A, Javed S, Guimbaud R, Rivera P, Karoui M, Auclin E, Taieb J. Hepatic Arterial Infusion Chemotherapy With Folfirinox or Oxaliplatin Alone in Metastatic Colorectal Cancer. Front Med (Lausanne) 2022; 9:830595. [PMID: 35783637 PMCID: PMC9243466 DOI: 10.3389/fmed.2022.830595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/05/2022] [Indexed: 12/04/2022] Open
Abstract
Background Hepatic arterial infusion (HAI) of chemotherapy is an option for the treatment of patients with liver metastases from colorectal cancer (LMCRC). Though HAI with oxaliplatin (HAI-Ox) is generally used, intravenous (IV) 5-fluoro-uracil (5FU)-oxaliplatin-irinotecan HAI (HAI-Folfirinox) is feasible and leads to curative-intent surgery in 30% of pretreated patients. We compared the efficacy and safety of HAI-Ox and HAI-Folfirinox. Methods Patients who underwent HAI chemotherapy for LMCRC were retrospectively included from 2008 to 2019 from six French expert centers. Results Data were collected from 273 previously treated patients with LMCRC. Patients received HAI-Folfirinox (n = 52) or HAI-Ox (n = 221) combined with IV chemotherapy. The objective response rate (ORR) was 43.2% in patients with HAI-Folfirinox and 45.9% (ns) in patients with HAI-Ox. Median overall survival (OS) was 17 months (95% CI: 15–32.3) with HAI-Folfirinox and 26.2 months (95% CI: 19.4–34.4; p = 0.1) with HAI-Ox. Median progression-free survival (PFS) was 7.9 months (95% CI: 4.9–10.3) with HAI-Folfirinox and 6.4 months (95% CI: 6.0–7.7; p = 0.6) with HAI-Ox. The secondary liver resection rate was 35.6% with HAI-Folfirinox and 16.7% with HAI-Ox (p = 0.007). Grade 2 and above toxicities were significantly more frequent with HAI-Folfirinox. In the global population, only 2 factors were prognostic for OS in multivariable analyses: liver-only disease [hazard ratio (HR): 0.4; 95% CI 0.20–0.83; p = 0.013] and local complications of the catheter (HR: 3.8; 95% CI 1.6–9.0; p = 0.002). Conclusion Hepatic arterial infusion results in high response rates, secondary resections, and long survival in pretreated patients with LMCRC.
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Affiliation(s)
- Violaine Randrian
- Department of Hepato-Gastro-Enterology, CHU Poitiers, Poitiers, France
| | - Simon Pernot
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France
| | | | - Denis Smith
- Medical Oncology, Bordeaux University Hospital, Bordeaux, France
| | - Annie Lim
- Department of Gastroenterology, Clinique Santé Atlantique, Saint-Herblain, France
| | - Yann Touchefeu
- Department of Hepatogastroenterology, Digestive Oncology, Nantes University Hospital, Nantes, France
| | - Claire Gallois
- Department of Gastrointestinal Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | | | - Sahir Javed
- Department of Oncology, CHU Lille, Lille, France
| | - Rosine Guimbaud
- Department of Digestive Oncology, IUCT-Rangueil, CHU Toulouse, Toulouse, France
| | - Pascale Rivera
- Department of Digestive Oncology, IUCT-Rangueil, CHU Toulouse, Toulouse, France
| | - Mehdi Karoui
- Department of Surgical Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | - Edouard Auclin
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Bourgogne Franche-Comté University, INSERM, EFS BFC, UMR 1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
- Department of Medical Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | - Julien Taieb
- Department of Gastrointestinal Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
- *Correspondence: Julien Taieb,
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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Pernot S, Pellerin O, Mineur L, Monterymard C, Smith D, Lapuyade B, Gallois C, Khemissa Akouz F, De Baere T, Tougeron D, Thirot-Bidault A, Audemar F, Simon M, Lecaille C, Louafi S, Lepage C, Ducreux M, Taieb J. Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49. Dig Liver Dis 2022; 54:324-330. [PMID: 35027324 DOI: 10.1016/j.dld.2021.12.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/14/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy. AIM The OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM. MATERIALS AND METHODS Main eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and <10 mm, ECOG performance status 0 or 1. ENDPOINT The primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life. CONCLUSION This study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).
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Affiliation(s)
- Simon Pernot
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
| | - Olivier Pellerin
- Department of Interventional Radiology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
| | - Laurent Mineur
- Department of Medical Oncology, Institut Sainte Catherine, Avignon, France
| | - Carole Monterymard
- Federation Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Denis Smith
- Department of Gastroenterology and GI Oncology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France
| | - Bruno Lapuyade
- Department of Interventional Radiology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France
| | - Claire Gallois
- Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
| | - Faiza Khemissa Akouz
- Department of Gastroenterology and GI Oncology, CH Saint-Jean, Perpignan, France
| | - Thierry De Baere
- Department of Interventional Radiology, Gustave Roussy, BIOTHERIS, Université Paris-Saclay, Villejuif, France
| | - David Tougeron
- Université de Poitiers, Department of Gastroenterology and Hepatology, CHU La Milétrie, Poitiers, France
| | | | - Franck Audemar
- Department of Gastroenterology and GI Oncology, CH de la Côte-Basque, Bayonne, France
| | - Mireille Simon
- Department of Gastroenterology and GI Oncology, CH Pau, Pau, France
| | - Cedric Lecaille
- Department of Gastroenterology and GI Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France
| | - Sami Louafi
- Department of Medical Oncology, CH Corbeille Essonne, France
| | - Come Lepage
- Federation Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France; Department of Gastroenterology and GI Oncology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France; Department of Interventional Radiology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France; Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France; Department of Gastroenterology and GI Oncology, CH Saint-Jean, Perpignan, France; Department of Interventional Radiology, Gustave Roussy, BIOTHERIS, Université Paris-Saclay, Villejuif, France; Université de Poitiers, Department of Gastroenterology and Hepatology, CHU La Milétrie, Poitiers, France; Department of Medical Oncology, Hôpital Privé d'Antony, Antony, France; Department of Gastroenterology and GI Oncology, CH de la Côte-Basque, Bayonne, France; Department of Gastroenterology and GI Oncology, CH Pau, Pau, France; Department of Gastroenterology and GI Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France; Department of Medical Oncology, CH Corbeille Essonne, France; Department of Gastroenterology and GI oncology, CHU Le Bocage, University of Burgundy and Franche Comté, Dijon, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Inserm U1279, Université Paris-Saclay, Villejuif, France
| | - Julien Taieb
- Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
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Torres-Jiménez J, Esteban-Villarrubia J, Ferreiro-Monteagudo R, Carrato A. Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist. Cancers (Basel) 2021; 13:5938. [PMID: 34885047 PMCID: PMC8656541 DOI: 10.3390/cancers13235938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 12/12/2022] Open
Abstract
For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
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Affiliation(s)
- Javier Torres-Jiménez
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Jorge Esteban-Villarrubia
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Reyes Ferreiro-Monteagudo
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Alfredo Carrato
- Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, 28034 Madrid, Spain;
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Druet A, Mosnier JF, Corbineau E, Matysiak-Budnik T, Touchefeu Y, Viala C. Defibrotide for Sinusoidal Obstruction Syndrome and Nodular Regenerative Hyperplasia After Oxaliplatin-Based Hepatic Intra-Arterial Chemotherapy: A Case Report. Clin Colorectal Cancer 2021; 21:e98-e101. [PMID: 34776359 DOI: 10.1016/j.clcc.2021.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 10/05/2021] [Accepted: 10/13/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Amaury Druet
- Institut des Maladies de l'Appareil Digestif, Digestive Oncology Unit, University Hospital, Nantes, France
| | | | | | - Tamara Matysiak-Budnik
- Institut des Maladies de l'Appareil Digestif, Digestive Oncology Unit, University Hospital, Nantes, France
| | - Yann Touchefeu
- Institut des Maladies de l'Appareil Digestif, Digestive Oncology Unit, University Hospital, Nantes, France.
| | - Caroline Viala
- Institut des Maladies de l'Appareil Digestif, Digestive Oncology Unit, University Hospital, Nantes, France
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21
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Fohlen A, Bordji K, Assenat E, Gongora C, Bazille C, Boulonnais J, Naveau M, Breuil C, Pérès EA, Bernaudin M, Guiu B. Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time. Pharmaceuticals (Basel) 2021; 14:ph14070639. [PMID: 34358065 PMCID: PMC8308869 DOI: 10.3390/ph14070639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 12/24/2022] Open
Abstract
To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC50 and IC90 were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI90 = C Max/IC90) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
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Affiliation(s)
- Audrey Fohlen
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Urodigestive Imagery and Interventional Radiology Department, University Hospital of Caen, CEDEX, 14000 Caen, France
- Correspondence: ; Tel.: +33-616702414
| | - Karim Bordji
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Eric Assenat
- Medical Oncology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
| | - Céline Gongora
- IRCM, Montpellier Cancerology Research Center, INSERM U1194, Montpellier University, Montpellier Regional Institute of Cancer, 34298 Montpellier, France;
| | - Céline Bazille
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Department of Pathology, University Hospital of Caen, CEDEX, 14000 Caen, France
| | - Jérémy Boulonnais
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Mikaël Naveau
- UNICAEN, CNRS, UMS 3408, GIP CYCERON, Normandie University, 14000 Caen, France;
| | - Cécile Breuil
- Pharmacy Department, University Hospital of Caen, CEDEX, 14000 Caen, France;
| | - Elodie A. Pérès
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Myriam Bernaudin
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Boris Guiu
- Radiology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
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22
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Zhao JJ, Tan E, Sultana R, Syn NL, Da Zhuang K, Leong S, Tai DWM, Too CW. Intra-arterial therapy for unresectable colorectal liver metastases: A meta-analysis. J Vasc Interv Radiol 2021; 32:1536-1545.e38. [PMID: 34166803 DOI: 10.1016/j.jvir.2021.05.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 05/09/2021] [Accepted: 05/31/2021] [Indexed: 11/19/2022] Open
Abstract
PURPOSE To evaluate the efficacy of hepatic arterial infusion (HAI), conventional trans-arterial chemoembolization (cTACE), drug-eluting embolic trans-arterial chemoembolization (DEE-TACE), trans-arterial radioembolization (TARE) and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases. METHODS A search was conducted on EMBASE, Scopus, PubMed and Web of Science for prospective non-randomized studies and randomized controlled trials (RCTs) from inception to 20th June 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for median overall survival (OS), survival rates (SR), and restricted mean survival time (RMST), while two-stage meta-analyses of proportions were conducted to determine response rates (RR) and conversion-to-resection rates (CRR). RESULTS 71 prospective non-randomized studies and 21 RCTs were identified comprising 6,695 patients. Among patients treated beyond first line, DEE-TACE+SCT (n=152) had the best survival outcomes of median OS of 26.5 (95%-CI: 22.5-29.1) months and 3-year RMST of 23.6 (95%-CI: 21.8-25.5) months. Upon further stratification by publication year, DEE-TACE+SCT appears to consistently have the highest pooled survival rates at 1-year (81.9%) and 2-years (66.1%) in recent publications (2015-2020). DEE-TACE+SCT and HAI+SCT had the highest pooled-RRs of 56.7% (I2=0.90) and 62.6% (I2=0.87) respectively and pooled-CRRs of 35.5% (I2=0.00) and 30.3% (I2=0.80) respectively. CONCLUSION Albeit significant heterogeneity, paucity of high-quality evidence and the non-comparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE+SCT may have the best oncological outcomes and greatest potential to be converted for resection.
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Affiliation(s)
- Joseph J Zhao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Eelin Tan
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - Rehena Sultana
- Centre for Quantitative Medicine, Duke-National University of Singapore Graduate Medical School, Singapore
| | - Nicholas L Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kun Da Zhuang
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - Sum Leong
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - David W M Tai
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Chow Wei Too
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore.
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Mauri G, Monfardini L, Garnero A, Zampino MG, Orsi F, Della Vigna P, Bonomo G, Varano GM, Busso M, Gazzera C, Fonio P, Veltri A, Calandri M. Optimizing Loco Regional Management of Oligometastatic Colorectal Cancer: Technical Aspects and Biomarkers, Two Sides of the Same Coin. Cancers (Basel) 2021; 13:2617. [PMID: 34073585 PMCID: PMC8198296 DOI: 10.3390/cancers13112617] [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: 02/22/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/23/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin.
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Affiliation(s)
- Giovanni Mauri
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
- Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, 20122 Milan, Italy
| | | | - Andrea Garnero
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
| | - Maria Giulia Zampino
- Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy;
| | - Franco Orsi
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Paolo Della Vigna
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Guido Bonomo
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Gianluca Maria Varano
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Marco Busso
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
| | - Carlo Gazzera
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Paolo Fonio
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Andrea Veltri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
| | - Marco Calandri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
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Kwan J, Pua U. Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis. Cancers (Basel) 2021; 13:cancers13061371. [PMID: 33803606 PMCID: PMC8003062 DOI: 10.3390/cancers13061371] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/14/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.
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Deschamps F, Tselikas L, Tasaki M, Motoyama S, Isoardo T, Ducreux M, Paunovic D, Moine L, de Baere T. Sustained-hepatic arterial infusion of oxaliplatin: pharmacokinetic advantages over hepatic arterial infusion using a preclinical animal tumour model. Drug Deliv Transl Res 2021; 11:2144-2150. [PMID: 33432522 DOI: 10.1007/s13346-020-00881-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2020] [Indexed: 11/28/2022]
Abstract
Hepatic arterial infusion (HAI) of oxaliplatin allows greater liver tumour drug exposure compared to systemic infusion. However, the therapeutic index of HAI oxaliplatin remains poor. Using Pickering emulsion technology, we developed a platform able to provide sustained releases of oxaliplatin. The goal of this study was to evaluate the pharmacokinetic advantages of sustained-HAI oxaliplatin over HAI using a preclinical animal tumour model. Injections of 0.6 mg oxaliplatin in 20 min were selectively done in left hepatic arteries of 20 rabbits bearing a VX2 liver tumour in the middle left-lobe, using HAI (n = 10) or sustained-HAI (n = 10). In each group, half of the rabbits were sacrificed at 24 h and half at 72 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and oxaliplatin concentrations in tumour tissues, right- and middle left-liver lobes, spleen and lung. Compared to HAI, sustained-HAI of oxaliplatin resulted in lower plasmatic peak (Cmax: 275 ± 41 vs. 416 ± 133 ng/mL, p = 0.02) and higher concentration in the tumour at 24 h (2118 ± 2107 vs. 210 ± 93 ng/g, p = 0.008). After HAI, oxaliplatin concentration in tumours was significantly higher than in lung at 24 h (p = 0.03) but no other difference was found between oxaliplatin concentrations in tumours and in liver lobes, spleen or lung, neither at 24 h nor at 72 h. On the opposite, sustained-HAI resulted in higher concentrations of oxaliplatin in tumour compared to oxaliplatin concentrations in the middle left lobe (163 ± 86 ng/g at 24 h, p = 0.01, and 90 ± 15 ng/g at 72 h, p = 0.04), right lobe (174 ± 112 ng/g at 24 h, p = 0.01, and 112 ± 35 ng/g, p = 0.04 at 72 h), spleen (142 ± 21 ng/g at 24 h, p = 0.01, and 98 ± 12 ng/g at 72 h, p = 0.04), and lung (85 ± 11 ng/g at 24 h, p = 0.01, and 52 ± 4 ng/g at 72 h, p = 0.03). Sustained-HAI improves the therapeutic index of HAI oxaliplatin and offers a great potential for patients suffering from unresectable colorectal liver metastases or hepatocellular carcinoma.
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Affiliation(s)
| | - Lambros Tselikas
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Laboratory of Translational Research in Immunology (LTRI), UMR 1015, Gustave Roussy, Villejuif, France
| | | | | | - Thomas Isoardo
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Laboratory of Translational Research in Immunology (LTRI), UMR 1015, Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Oncology department, Gustave Roussy, Villejuif, France.,Université Paris-Saclay, Saint-Aubin, France
| | - Dragica Paunovic
- Global Medical Affairs, Terumo Corporation, Interventional Systems, Tokyo, Japan
| | - Laurence Moine
- Institut Galien, CNRS. Paris-Sud University, Châtenay-Malabry, France
| | - Thierry de Baere
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Université Paris-Saclay, Saint-Aubin, France
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Connell LC, Kemeny NE. Intraarterial Chemotherapy for Liver Metastases. Surg Oncol Clin N Am 2021; 30:143-158. [PMID: 33220802 PMCID: PMC8594481 DOI: 10.1016/j.soc.2020.08.005] [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] [Indexed: 10/23/2022]
Abstract
Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.
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Affiliation(s)
- Louise C Connell
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA.
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Surg Oncol Clin N Am 2021; 30:1-25. [PMID: 33220799 DOI: 10.1016/j.soc.2020.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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Dall'Armellina F, Perret A, Smolenschi C, Hollebecque A, Malka D, Boige V, Ducreux M. Hepatic arterial infusion of chemotherapy as an option in a multimodal treatment of metastatic squamous cell carcinoma of the anus. Eur J Cancer 2020; 142:147-149. [PMID: 33268233 DOI: 10.1016/j.ejca.2020.09.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 09/23/2020] [Indexed: 12/01/2022]
Affiliation(s)
- François Dall'Armellina
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France; Cliniques Universitaires Saint-Luc, Brussels, Belgium; Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
| | - Audrey Perret
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | | | | | - David Malka
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | - Valérie Boige
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
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Hepatic arterial infusion of oxaliplatin plus systemic chemotherapy and targeted therapy for unresectable colorectal liver metastases. Eur J Cancer 2020; 138:89-98. [PMID: 32871526 DOI: 10.1016/j.ejca.2020.07.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 07/19/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatic arterial infusion (HAI) combined with systemic chemotherapy has shown promising results in patients with unresectable colorectal liver metastases (CRLM), even after failure to systemic therapy. Addition of systemic targeted therapies has been investigated with controversial results regarding tolerance, especially with HAI-floruxidine when combined with systemic bevacizumab. Our study aimed to analyse feasibility, safety and efficacy of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies. METHODS Between 2005 and 2016, single-centre consecutive patients with unresectable CRLM who received at least one cycle of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies (cetuximab/panitumumab or bevacizumab) were analysed. RESULTS A total of 89 patients (median age 55 years (range, 26-76 years) who previously received a median number of one systemic chemotherapy regimen (range, 0-5) including oxaliplatin in 78% of cases were included. Median number of HAI-oxaliplatin cycles was 9 (range, 1-28) combined with systemic chemotherapy and targeted therapies (LV5FU2 [63%], FOLFIRI [36%]) plus anti-EGFR (30%), or bevacizumab (70%). Grade 3/4 toxicities included neutropenia (40%), HAI-related abdominal pain (43%) and neurotoxicity (12%). The intent-to-treat objective response rate was 42%, and 45% had stable disease, allowing complete CRLM resection/ablation in 27% of patients. After a median follow-up of 72 months, median overall and progression-free survival was 20 and 9 months, respectively. CONCLUSION Addition of targeted therapy to systemic chemotherapy combined with HAI-oxaliplatin is feasible, safe and shows promising activity, even after systemic chemotherapy failure.
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Datta J, Narayan RR, Kemeny NE, D'Angelica MI. Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review. JAMA Surg 2020; 154:768-776. [PMID: 31188415 DOI: 10.1001/jamasurg.2019.1694] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Importance Although liver metastasis develops in more than half of patients with colorectal cancer, only 15% to 20% of these patients have resectable liver metastasis at presentation. Moreover, patients with initially unresectable colorectal liver metastasis (IU-CRLM) who progress on first-line systemic chemotherapy have limited treatment options. Hepatic arterial infusion chemotherapy (HAIC), in combination with systemic chemotherapy, leverages a multimodality approach to achieving control of hepatic disease and/or expanding resectability in patients with liver-only disease or liver-dominant disease. Observations Intra-arterial delivery of agents with high first-pass hepatic extraction (eg, floxuridine) limits systemic toxic effects and allows for administration of systemic chemotherapy at near-full doses. Hepatic arterial infusion chemotherapy in conjunction with systemic chemotherapy augments response rates up to 92% in patients who are chemotherapy naive, and up to 85% in pretreated patients with IU-CRLM. In turn, these responses translate into encouraging rates of conversion to resectability (CTR). Prospective trials have reported CTR rates as high as 52% in heavily pretreated patients with IU-CRLM who have an extensive hepatic disease burden. As such, CTR remains a compelling indication for liver-directed chemotherapy in this subset of patients. This review discusses the biological rationale for HAIC, evolution of rational combinations with systemic chemotherapy, contemporary evidence for CTR using HAIC and systemic chemotherapy, juxtaposition with rates of CTR using systemic chemotherapy alone, and morbidity and toxic effect profiles of HAIC. Conclusions and Relevance The argument is made for consideration of earlier initiation of HAIC in patients with IU-CRLM who are chemotherapy naive and for adoption of HAIC strategies to augment rates of resectability in patients who have failed first-line systemic chemotherapy before proceeding to second-line or third-line regimens.
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Affiliation(s)
- Jashodeep Datta
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Raja R Narayan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Long GB, Xiao CW, Zhao XY, Zhang J, Li X. Effects of hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2020; 99:e20745. [PMID: 32590750 PMCID: PMC7328911 DOI: 10.1097/md.0000000000020745] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The potential benefits and safety of hepatic arterial infusion chemotherapy (HAIC) for the treatment of patients with hepatocellular carcinoma (HCC) remains inconsistent. Therefore, we conducted this meta-analysis of evaluate the efficacy and safety of HAIC in the treatment of HCC. METHODS A comprehensive literature search was performed using PubMed, Embase, Web of Science, and the Cochrane library to identify eligible studies that compared HAIC with other therapies for patients with HCC. The main outcomes of our interest, including overall survival (OS), disease free survival (DFS), objective response rate (ORR), disease control rate (DCR), and adverse events, were calculated using the meta-analysis. The pooled estimates were expressed with hazard ratio (HR) with 95%confidence intervals (95%CIs) or risk ratio (RR) with 95%CIs. RESULTS A total of 13 studies met the inclusion criteria and were included in this meta-analysis. Pooled estimates showed that, HAIC was associated with significantly improved OS (HR = 0.61, 95%CI: 0.48, 0.77; P < .001) and DFS (HR = 0.66, 95%CI: 0.52, 0.84; P = .001) as compared with other therapies. The ORR (RR = 2.28, 95%CI: 1.77, 2.94; P < .001) and DCR (RR = 1.47, 95%CI: 1.23, 1.77; P < .001) were also significantly higher in HAIC group than in control group. Most of the common adverse events were comparably occurred in the 2 groups, except for nausea/vomiting, hypoalbuminemia, pain, anemia and hepatic toxicity. Subgroup analysis suggested that, the improved OS and DFS associated with HAIC were only observed in patients with colorectal liver metastases (CRLM), or advanced HCC, but not in those with unresectable HCC or pancreatic liver metastases. CONCLUSION Based on the present data, HAIC showed benefit effect in HCC patients, with pronged OS and DFS, as well as increased ORR and DCR. These benefit effects were more obvious in CRLM or advanced HCC patients. However, considering the potential limitations, more large-scale, randomized trials are needed to verify our findings.
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Sato Y, Inaba Y, Aramaki T, Sone M, Morita Y, Nishiofuku H, Tanaka T, Miyazaki M, Matsueda K, Arai Y. Hepatic Arterial Infusion Chemotherapy of 5-Fluorouracil for Patients with Unresectable Liver Metastases from Colorectal Cancer Refractory to Standard Systemic Chemotherapy: A Multicenter Retrospective Study. Oncology 2020; 98:267-272. [PMID: 32092755 DOI: 10.1159/000505520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 12/17/2019] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Hepatic arterial infusion chemotherapy (HAIC) is a feasible treatment for patients with colorectal cancer (CRC) with unresectable liver metastases. OBJECTIVE The aim of this retrospective study was to assess HAIC of 5-fluorouracil (5FU) in patients with unresectable liver metastases from CRC refractory to standard systemic chemotherapy. METHODS A total of 137 patients (85 men, 52 women; median age, 62 years; with KRAS mutation, n = 57) were recruited from seven institutions from September 2008 to December 2015. These patients were refractory to systemic chemotherapy including three cytotoxic agents (fluoropyrimidine, oxaliplatin, and irinotecan) with two molecular-targeted agents (bevacizumab and epidermal growth factor receptor antibody [cetuximab or panitumumab]). All patients underwent HAIC of continuous 5FU for unresectable liver metastases. Overall survival time, time to treatment failure, objective response rate, disease control rate, and incidence of adverse events to HAIC were assessed retrospectively. RESULTS The median overall survival time was 4.8 months (95% confidence interval [CI], 4.0-5.7 months), whereas time to treatment failure was 2.4 months (95% CI, 2.0-2.8 months). The objective overall response rate and disease control rate were 12.4 and 64%, respectively. Grade 3 or 4 adverse events were observed in 2.9% of the patients (hyperbilirubinemia in 2, liver abscess in 1, and myelosuppression in 1). CONCLUSIONS There were few incidences of severe adverse events to HAIC of 5FU for liver metastases from CRC refractory to standard systemic chemotherapy. Therefore, it might present as a treatment option as last-line chemotherapy.
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Affiliation(s)
- Yozo Sato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan,
| | - Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takeshi Aramaki
- Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Miyuki Sone
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshitaka Morita
- Department of Diagnostic Radiology, Kobe Medical Center, Kobe, Japan
| | | | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, Kashihara, Japan
| | - Masaya Miyazaki
- Department of Interventional Radiology and Clinical Ultrasound Center, Gunma University Hospital, Maebashi, Japan
| | - Kiyoshi Matsueda
- Diagnostic Imaging Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yasuaki Arai
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
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Boilève A, Maillard A, Wagner M, Dromain C, Laurent C, Dupont Bierre E, Le Sourd S, Audemar F, Ulusakarya A, Guerin-Meyer V, Smisth D, Pezzella V, De Baere T, Goere D, Gelli M, Taieb J, Boige V. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol. BMC Cancer 2020; 20:74. [PMID: 32000724 PMCID: PMC6990591 DOI: 10.1186/s12885-020-6571-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 01/23/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10-15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT. OBJECTIVES AND ENDPOINTS OF THE PHASE II STUDY Our main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0). METHODS This study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients. TRIAL REGISTRATION ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.
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Affiliation(s)
- Alice Boilève
- Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.
| | - Aline Maillard
- Department of statistics and epidemiology, Villejuif, France.,Centre for Research in Epidemiology and Population Health (team 2), INSERM U1018, Paris-Saclay University, Villejuif, France
| | - Mathilde Wagner
- Department of radiology, CHU Pitié Salpétrière, Paris, France
| | - Clarisse Dromain
- Department of radiology, Centre Hospitalier et Universitaire Vaudois, Lausanne, Switzerland
| | - Christophe Laurent
- Department of hepatogastroenterology, Hôpital Haut Levêque, Pessac, France
| | - Eric Dupont Bierre
- Department of digestive surgery, CHP Saint Grégoire, Saint-Grégoire, France
| | - Samuel Le Sourd
- Department of medical oncology, Centre Eugène-Marquis, Rennes, France
| | - Franck Audemar
- Department of hepatogastroenterology, Centre hospitalier Côte Basque, Bayonne, France
| | - Ayhan Ulusakarya
- Department of medical oncology, Hôpital Paul Brousse, Villejuif, France
| | | | - Denis Smisth
- Department of hepatogastroenterology, Hôpital Haut Levêque, Pessac, France
| | | | - Thierry De Baere
- Department of interventional radiology, Gustave Roussy, Villejuif, France
| | - Diane Goere
- Department of Surgical Oncology, Hôpital Saint Louis, Paris, France
| | | | - Julien Taieb
- Department of digestive oncology, Hôpital Européen Georges-Pompidou, Sorbonne Paris Cite/Paris Descartes University, Paris, France
| | - Valérie Boige
- Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France
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Abrahamsson H, Jensen BV, Berven LL, Nielsen DL, Šaltytė Benth J, Johansen JS, Larsen FO, Johansen JS, Ree AH. Antitumour immunity invoked by hepatic arterial infusion of first-line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8-12 years of follow-up. Int J Cancer 2020; 146:2019-2026. [PMID: 31872440 DOI: 10.1002/ijc.32847] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/09/2019] [Accepted: 12/17/2019] [Indexed: 12/21/2022]
Abstract
In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
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Affiliation(s)
- Hanna Abrahamsson
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Benny V Jensen
- Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Lise L Berven
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Dorte L Nielsen
- Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark.,Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Jūratė Šaltytė Benth
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway
| | - Jakob S Johansen
- Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Finn O Larsen
- Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Julia S Johansen
- Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark.,Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Anne H Ree
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Phelip JM, Tougeron D, Léonard D, Benhaim L, Desolneux G, Dupré A, Michel P, Penna C, Tournigand C, Louvet C, Christou N, Chevallier P, Dohan A, Rousseaux B, Bouché O. Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig Liver Dis 2019; 51:1357-1363. [PMID: 31320305 DOI: 10.1016/j.dld.2019.05.035] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 05/28/2019] [Accepted: 05/30/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of Gastroenterology website (SNFGE) (www.tncd.org). METHODS This collaborative work was realized by all French medical and surgical societies involved in the management of mCRC. Recommendations are graded in three categories (A, B and C), according to the level of evidence found in the literature, up until December 2018. RESULTS The management of metastatic colorectal cancer has become complex because of increasing available medical, radiological and surgical treatments alone or in combination. The therapeutic strategy should be defined before the first-line treatment, mostly depending on the presentation of the disease (resectability of the metastases, symptomatic and/or threatening disease), of the patient's condition (ECOG PS, comorbidities), and tumor biology (RAS, BRAF, MSI). The sequence of targeted therapies also seems to have an impact on the outcome (angiogenesis inhibition beyond progression). Surgical resection of metastases was the only curative intent treatment to date, joined recently by percutaneous tumor ablation tools (radiofrequency, microwave). Localized therapies such as hepatic intra-arterial infusion, radioembolization and hyperthermic intraperitoneal chemotherapy, also have seen their indications specified (liver-dominant disease and resectable peritoneal carcinomatosis). New treatments have been developed in heavily pretreated patients, increasing overall survival and preserving quality of life (regorafenib and trifluridine/tipiracil). Finally, immune checkpoint inhibitors have demonstrated high efficacy in MSI mCRC. CONCLUSION French guidelines for mCRC management are put together to help offer the best personalized therapeutic strategy in daily clinical practice, as the mCRC therapeutic landscape is complexifying. These recommendations are permanently being reviewed and updated. Each individual case must be discussed within a multidisciplinary team (MDT).
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Affiliation(s)
- Jean Marc Phelip
- Department of Gastroenterology and Digestive Oncology, University Hospital of Saint Etienne, Saint Etienne, France.
| | - David Tougeron
- Department of Gastroenterology, University Hospital of Poitiers, Poitiers, France
| | - David Léonard
- Department of Surgical Oncology, Clinique de la Loire, Saumur, France
| | - Leonor Benhaim
- Department of Surgical Oncology, GustaveRoussy Cancer Center, UNICANCER, Villejuif, France
| | - Grégoire Desolneux
- Department of Surgical Oncology, Bergonie Institute, UNICANCER, Bordeaux, France
| | - Aurélien Dupré
- Department of Surgical Oncology, Leon Berard Cancer Center, UNICANCER, Lyon, France
| | - Pierre Michel
- Department of Gastroenterology and Digestive Oncology, University Hospital of Rouen, Rouen, France
| | - Christophe Penna
- Department of Surgical Oncology, Bicêtres Hospital, APHP, Paris, France
| | - Christophe Tournigand
- Department of Gastroenterology and Digestive Oncology, Henri-Mondor University Hospital, APHP, Creteil, France
| | - Christophe Louvet
- Department of Medical Oncology, Institut Mutualiste Montsouris (IMM), Paris, France
| | - Nikki Christou
- Department of Digestive, Endocrine and General Surgery, University Hospital of Limoges, France
| | | | - Anthony Dohan
- Department of Abdominal and Interventional Radiology, Cochin Unversity Hospital, APHP, Paris, France
| | - Benoist Rousseaux
- Department of Medical Oncology, Henri Mondor Hospital, APHP, Creteil, France; Memorial Sloan Kettering Cancer Center, Solid Tumor Department, New York, USA
| | - Olivier Bouché
- Department of Digestive Oncology, University Hospital of Reims, Reims, France
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Ghiringhelli F, Vincent J, Bengrine L, Borg C, Jouve JL, Loffroy R, Guiu B, Blanc J, Bertaut A. Hepatic arterial chemotherapy with raltitrexed and oxaliplatin versus standard chemotherapy in unresectable liver metastases from colorectal cancer after conventional chemotherapy failure (HEARTO): a randomized phase-II study. J Cancer Res Clin Oncol 2019; 145:2357-2363. [PMID: 31273511 DOI: 10.1007/s00432-019-02970-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 07/01/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Hepatic arterial infusion (HAI) of chemotherapy could be used in patients with liver-only metastatic colorectal cancer (mCRC) to fight against chemoresistance. We previously reported the efficacy of raltitrexed plus oxaliplatin (HAI) in a retrospective series. We performed a randomized two-stage phase-II study to evaluate the efficacy of HAI of the combination of raltitrexed and oxaliplatin in refractory mCRC with only liver metastases in comparison with standard of care. PATIENTS AND METHODS Eligible patients had unresectable mCRC and were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were randomized between HAI raltitrexed (3 mg/m2 over 1 h) followed by oxaliplatin (130 mg/m2 over 2 h) every 3 weeks and standard of care in a 2:1 ratio. A total of 57 patients (38 in the experimental arm and 19 in the standard of care arm) were to be included. The main objective was to demonstrate 6-month PFS of 45% by intention-to-treat analysis in the experimental arm, compared to theoretical PFS of 20%, with a unilateral alpha risk of 5% and beta risk of 10%. RESULTS After inclusion of 27 patients, the trial was terminated due to insufficient accrual. In the experimental arm, 11 and 4 patients experienced grade 3 and 4 toxicities, respectively. The most frequent grade 3-4 toxicities were neutropenia, liver toxicity, and abdominal pain. Median progression-free survival was 6.7 months (95% Confidence Interval; 3.9-7.2) in the HAI group and 2.2 months (95% CI 1.2-4.3) with standard of care [HR 0.32 (95% CI 0.14-0.76), p = 0.01]. Median overall survival did not differ between the two groups, at 11.2 months (95% CI 4.8-17.6) for the HAI group and 11.9 months (95% CI 2.8-14.3) for standard of care [HR 0.86 (95% CI 0.36-2.04), p = 0.73]. CONCLUSION Although stopped prematurely, this randomized trial provides evidence for the benefit and safety of HAI of a combination of raltitrexed and oxaliplatin in liver-only mCRC with chemoresistant disease.
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Affiliation(s)
- Francois Ghiringhelli
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France.
- University of Burgundy and Franche Comté, Dijon, France.
| | - Julie Vincent
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France
| | - Leila Bengrine
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France
| | - Christophe Borg
- University of Burgundy and Franche Comté, Dijon, France
- University Hospital of Besançon and CIC-BT506, Besançon, France
| | | | - Romaric Loffroy
- University of Burgundy and Franche Comté, Dijon, France
- University Hospital of Dijon, Dijon, France
| | - Boris Guiu
- University Hospital of Montpellier, Montpellier, France
| | - Julie Blanc
- Unit of Methodology and Biostatistics, Centre Georges-François Leclerc, Dijon, France
| | - Aurélie Bertaut
- Unit of Methodology and Biostatistics, Centre Georges-François Leclerc, Dijon, France
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Kemeny N, Kurilova I, Li J, Camacho JC, Sofocleous CT. Liver-Directed and Systemic Therapies for Colorectal Cancer Liver Metastases. Cardiovasc Intervent Radiol 2019; 42:1240-1254. [PMID: 31312902 DOI: 10.1007/s00270-019-02284-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 07/03/2019] [Indexed: 02/07/2023]
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40
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Larsen FO, Jensen BV, Nørgaard HH, Hermann HK, Larsen PN, Markussen A, Hogdall E, Nielsen D. Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer. Oncology 2019; 96:299-308. [PMID: 30999314 DOI: 10.1159/000499314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/28/2019] [Indexed: 01/26/2023]
Abstract
BACKGROUND In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. METHODS Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. RESULTS The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0-44.3) and 12.9 months (95% CI 10.2-15.6), respectively. CONCLUSIONS Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained.
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Affiliation(s)
- Finn Ole Larsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark,
| | - Benny V Jensen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Hans Henrik Nørgaard
- Department of Radiology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Bispebjerg and Frederiksberg, Denmark
| | - Helle Kirstine Hermann
- Department of Radiology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Peter N Larsen
- Department of Liver Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Alice Markussen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Estrid Hogdall
- Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Dorte Nielsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
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Oxaliplatin-Based Intra-arterial Chemotherapy in Colo-Rectal Cancer Liver Metastases: A Review from Pharmacology to Clinical Application. Cancers (Basel) 2019; 11:cancers11020141. [PMID: 30682873 PMCID: PMC6406804 DOI: 10.3390/cancers11020141] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 01/18/2019] [Accepted: 01/22/2019] [Indexed: 01/04/2023] Open
Abstract
Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion (HAI) of antitumor drugs deeply modifies the treatment of LMCRC due to the knowledge that LM are perfused by the hepatic artery network, whereas healthy tissue is perfused by the portal vein. Therefore, oxaliplatin-based HAI becomes an interesting possibility to treat LMCRC. The aim of this review is to shed light on the important impact of the oxaliplatin-based chemotherapy from a non-conventional clinical point of view, considering that, being universally accepted its antitumor effect if administered intravenously, fragmentary information are known about its clinical applications and benefits deriving from intra-arterial administration in loco-regional chemotherapy.
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Fountzilas E, Krishnan E, Janku F, Fu S, Karp DD, Naing A, Subbiah V, Hong DS, Piha-Paul SA, Vining DJ, Tsimberidou AM. A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. Cancer Chemother Pharmacol 2018; 82:877-885. [PMID: 30182147 DOI: 10.1007/s00280-018-3680-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 08/27/2018] [Indexed: 01/25/2023]
Abstract
BACKGROUND We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement. METHODS Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. RESULTS From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2). CONCLUSION HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.
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Affiliation(s)
- Elena Fountzilas
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Elangovan Krishnan
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Filip Janku
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Siqing Fu
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Daniel D Karp
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Aung Naing
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Vivek Subbiah
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David S Hong
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Sarina A Piha-Paul
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David J Vining
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Apostolia-Maria Tsimberidou
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Gavriilidis P, Tobias A, Sutcliffe RP, Azoulay D, Roberts KJ. Network Meta-Analysis of Adjuvant Chemotherapy following Resection of Colorectal Liver Metastases. Gastrointest Tumors 2018; 5:21-31. [PMID: 30574478 PMCID: PMC6288637 DOI: 10.1159/000490763] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 06/05/2018] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Six principal adjuvant chemotherapy treatments (ACTs) are currently available for patients with resected colorectal liver metastases. This meta-analysis was designed to determine the optimal ACT, as evaluated by 2-year disease-free survival (DFS) and 5-year overall survival (OS) rates as well as by hepatic recurrences and adverse events (AEs). METHODS A systematic literature search of the PubMed, EMBASE, Medline, Cochrane Library, and Google Scholar databases was performed. The probability of the optimal therapeutic scheme and the mean ranking were estimated for each treatment using network meta-analysis. RESULTS Systemic chemotherapy (SCT) had the best 2-year DFS rate (hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.48-1.27, 95% prediction interval [PI] = 0.17-3.56, surface under the cumulative ranking area [SUCRA] = 73) and the lowest AE rate (estimated SUCRA = 65 and predicted SUCRA = 62). Hepatic arterial infusion (HAI) plus SCT had the best 5-year OS rate (HR = 0.81, 95% CI = 0.64-1.01, 95% PI = 0.50-1.29) and the lowest hepatic recurrence rate (odds ratio = 2.87, 95% CI = 1.56-5.30, 95% PI = 0.61-13.62). CONCLUSION Both SCT and HAI plus SCT showed superior efficacy and safety. Clinical trials in homogeneous populations with strict selection criteria are needed to compare these two ACTs.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Aurelio Tobias
- Biostatistician in the Spanish Council for Scientific Research (CSIC), Barcelona, Spain
| | - Robert P. Sutcliffe
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Daniel Azoulay
- Department of Hepato-Pancreato-Biliary and Liver Transplantation, Henri Mondor University Hospital, Créteil, France
| | - Keith J. Roberts
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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Goéré D, Pignon JP, Gelli M, Elias D, Benhaim L, Deschamps F, Caramella C, Boige V, Ducreux M, de Baere T, Malka D. Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial - PACHA-01 (NCT02494973). BMC Cancer 2018; 18:787. [PMID: 30081865 PMCID: PMC6080555 DOI: 10.1186/s12885-018-4697-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 07/26/2018] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND After curative-intent surgery for colorectal liver metastases (CRLM), liver recurrence occurs in more than 60% of patients, despite the administration of perioperative or adjuvant chemotherapy. This risk is even higher after resection of more than three CRLM. As CRLM are mostly supplied by arterial blood flow, hepatic arterial infusion (HAI) of chemotherapeutic agents after resection of CRLM is an attractive approach. Oxaliplatin-based HAI chemotherapy, in association with systemic fluoropyrimidines, has been shown to be safe and highly active in patients with CRLM. In a retrospective series of 98 patients at high risk of hepatic recurrence (≥4 resected CRLM), adjuvant HAI oxaliplatin combined with systemic chemotherapy was feasible and significantly improved disease-free survival compared to adjuvant, 'modern' systemic chemotherapy alone. METHODS/DESIGN This study is designed as a multicentre, randomized, phase II/III trial. The first step is a non-comparative randomized phase II trial (power, 95%; one-sided alpha risk, 10%). Patients will be randomly assigned in a 1:1 ratio to adjuvant systemic FOLFOX (control arm) or adjuvant HAI oxaliplatin plus systemic LV5FU2 (experimental arm). A total 114 patients will need to be included. The main objective of this trial is to evaluate the potential survival benefit of adjuvant HAI with oxaliplatin after resection of at least 4 CRLM (primary endpoint: 18-month hepatic recurrence-free survival rate). We also aim to assess the feasibility of delivering at least 4 cycles of HAI (or i.v.) oxaliplatin after surgical treatment of at least 4 CRLM, the toxicity (NCI-CTC v4.0) of adjuvant HAI plus systemic chemotherapy, including HAI catheter-related complications, compared to systemic chemotherapy alone, and the efficacy of adjuvant HAI on hepatic and extra-hepatic recurrence-free (survival and overall survival). DISCUSSION If 18-month hepatic recurrence-free survival is greater than 50% in the experimental arm, the study will be pursued in phase III, for which the primary endpoint will be 3-year recurrence-free survival rate. Patients randomized in the phase II will be included in the phase III, with an additional number of 106 patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02494973 . Trial registration date: July 10, 2015.
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Affiliation(s)
- Diane Goéré
- Department of Surgical Oncology - Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.
| | - Jean-Pierre Pignon
- Statistics and Epidemiology Unit - Gustave Roussy, Villejuif, France.,Centre for Research in Epidemiology and Population Health (team 2), INSERM U1018, Paris-Saclay University, Villejuif, France
| | - Maximiliano Gelli
- Department of Surgical Oncology - Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France
| | - Dominique Elias
- Department of Surgical Oncology - Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France
| | - Léonor Benhaim
- Department of Surgical Oncology - Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France
| | - Frédéric Deschamps
- Department of Interventional Radiology - Gustave Roussy, Villejuif, France
| | | | - Valérie Boige
- Department of Cancer Medicine - Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Department of Cancer Medicine - Gustave Roussy, Villejuif, France
| | - Thierry de Baere
- Department of Interventional Radiology - Gustave Roussy, Villejuif, France
| | - David Malka
- Department of Cancer Medicine - Gustave Roussy, Villejuif, France
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Pernot S, Velut G, Kourie RH, Amouyal G, Sapoval M, Pointet AL, Landi B, Zaimi Y, Lepère C, Pellerin O, Taieb J. 5-FU or mitomycin C hepatic arterial infusion after failure of arterial oxaliplatin in patients with colorectal cancer unresectable liver metastases. Clin Res Hepatol Gastroenterol 2018; 42:255-260. [PMID: 29233520 DOI: 10.1016/j.clinre.2017.11.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 10/27/2017] [Accepted: 11/13/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hepatic arterial infusion (HAI) chemotherapy with oxaliplatin is an accepted option in the management of colorectal cancer (CRC) with dominant liver metastases (LM). However, despite prolonged control, some patients experience disease progression. On the other hand, oxaliplatin leads to dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. We evaluated treatment outcomes in patients receiving second-line HAI with 5-FU or mitomycin C, after first-line HAI of oxaliplatin in heavily pretreated patients. MATERIAL AND METHODS Between March 2010 and June 2016, this observational study included 24 patients with unresectable CRC LM and treated with HAI of 5-FU (17 patients) or mitomycin C (7 patients), after HAI of oxaliplatin. RESULTS Mean age was 61.7 years. Forty-two percent of patients (10/24) had extra-hepatic metastases and 75% (18/24) at least 8 liver metastases. Including HAI of oxaliplatin, all patients had previously received at least 2 lines of chemotherapy±targeted agents (100%) and 96% (23/24) received concomitant systemic therapies together with HAI of 5-FU or mitomycin C. The overall objective response rate and disease control rate were, respectively, 42% (10/24) and 71% (17/24). Median progression-free survival and overall survival (OS) were, respectively, 5.6 and 25.8 months; hepatic progression-free survival was 8.5months. Thirteen percent (3/24) of the patients received further curative intent treatment after HAI 5-FU and mitomycin C. No toxic death occurred and the toxicity profile was acceptable. CONCLUSIONS HAI of 5-FU or mitomycin C is an alternative option in patients with predominant CRC LM, when they experience disease progression or do not tolerate HAI of oxaliplatin.
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Affiliation(s)
- Simon Pernot
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Guillaume Velut
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Rapahel Hampig Kourie
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Gregory Amouyal
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Marc Sapoval
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Anne Laure Pointet
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Bruno Landi
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Yosra Zaimi
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Céline Lepère
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Olivier Pellerin
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Julien Taieb
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France.
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Chapelle N, Matysiak-Budnik T, Douane F, Metairie S, Rougier P, Touchefeu Y. Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives. Dig Liver Dis 2018; 50:220-225. [PMID: 29290599 DOI: 10.1016/j.dld.2017.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 12/04/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
The technique of hepatic arterial infusion (HAI) for the treatment of liver metastases from colorectal cancer has been developed over more than 30 years. Although the indications and protocols for this technique have evolved with time, HAI is not routinely performed in clinical practice. Studies have been heterogeneous, with different regimens of intra-arterial drugs, associated or not with systemic chemotherapy, and with unconvincing outcomes. Technical difficulties for catheter placement have limited the implementation of this method in routine practice. The aim of this review is to present recent studies, highlighting technical improvements and promising combinations of oxaliplatin-based HAI with systemic treatments. HAI is being investigated in both the metastatic setting - in the first line and beyond - and in the adjuvant setting, and we will discuss its potential place in current and future patient management.
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Affiliation(s)
- Nicolas Chapelle
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France.
| | - Tamara Matysiak-Budnik
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | | | | | - Philippe Rougier
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | - Yann Touchefeu
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
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Deschamps F, Harris KR, Moine L, Li W, Tselikas L, Isoardo T, Lewandowski RJ, Paci A, Huang N, de Baere T, Salem R, Larson AC. Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. Cardiovasc Intervent Radiol 2018; 41:781-788. [PMID: 29468287 DOI: 10.1007/s00270-018-1899-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 02/07/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. MATERIALS/METHODS Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. RESULTS Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). CONCLUSION Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.
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Affiliation(s)
- Frederic Deschamps
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France. .,CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France.
| | | | - Laurence Moine
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Weiguo Li
- Department of Radiology, Northwestern University, Chicago, USA
| | - Lambros Tselikas
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Thomas Isoardo
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | | | - Angelo Paci
- CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France
| | - Nicolas Huang
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Thierry de Baere
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Riad Salem
- Department of Radiology, Northwestern University, Chicago, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Chicago, USA
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Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study. Clin Colorectal Cancer 2017; 16:308-315. [DOI: 10.1016/j.clcc.2017.03.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 02/19/2017] [Accepted: 03/01/2017] [Indexed: 01/05/2023]
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Abstract
INTRODUCTION Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions. Areas covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases. This article reviews the liver-directed therapeutic strategies available for the management of metastatic liver disease including hepatic arterial infusion therapy, radiofrequency ablation, radiation therapy and transarterial chemoembolization. Expert commentary: Great advances have been made with the use of liver directed therapies. In the USA using hepatic arterial infusions with FUDR and Decadron along with systemic therapy, 5 year survivals after liver resection have improved. In Europe with the use of HAI of Oxaliplatin, more patients have been able to get to resection and have obtained higher survival rates, even in second line therapy. New advances in ablative therapy have improved results to get all disease treated at resection for the treatment of reccurrence.
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Affiliation(s)
- Ciara M Kelly
- a Department of Graduate Medical Education , Memorial Sloan Kettering Cancer Center , New York , USA
| | - Nancy E Kemeny
- b Memorial Sloan-Kettering Cancer Center , Weill Medical College of Cornell University , New York , USA
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50
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Volovat SR, Volovat C, Negru SM, Danciu M, Scripcariu V. The efficacy and safety of hepatic arterial infusion of oxaliplatin plus intravenous irinotecan, leucovorin and fluorouracil in colorectal cancer with inoperable hepatic metastasis. J Chemother 2017; 28:235-41. [PMID: 26018108 DOI: 10.1179/1973947815y.0000000042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85 mg/m(2) HAI plus systemic intravenous chemotherapy [leucovorin 200 mg/m(2), 5-FU 2400 mg/m(2) and irinotecan (IRI) 160 mg/m(2) in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.
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Affiliation(s)
- Simona R Volovat
- a Regional Institute of Oncology , University of Medicine and Pharmacy 'Gr.T.Popa' , Iasi , Romania
| | | | - Serban M Negru
- c University of Medicine and Pharmacy Timisoara , Romania
| | - Mihai Danciu
- d University Hospital 'St. Spiridon' , University of Medicine and Pharmacy 'Gr.T.Popa' , Iasi , Romania
| | - Viorel Scripcariu
- a Regional Institute of Oncology , University of Medicine and Pharmacy 'Gr.T.Popa' , Iasi , Romania
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