A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: A Hellenic Cooperative Oncology Group study

BMC Medicine

Research Article

Dimitrios Bafaloukos¹  George Basdanis²  George Klouvas³  Dimitrios Pectasides⁴  Nikolaos Xiros⁴  Theofanis Economopoulos⁴  Charisios Karanikiotis⁵  Lia Malettou⁶  Meletios A Dimopoulos⁷  Aristotelis Bamias⁷  Christos A Papadimitriou⁷  Nikolaos Pisanidis⁸  George Pentheroudakis⁹  Maria Karina^1,10  Ippokratis Korantzis^1,10  George Fountzilas^1,10  Georgia Kafiri^1,11  Ioannis Efstratiou^1,12  Thomas Makatsoris^1,13  Haralabos P Kalofonos^1,13  Irene Papaspirou^1,14  Dimosthenis Miliaras^1,15  Pavlos Papakostas^1,16  Fotini Matsiakou^1,16  Epaminontas Samantas^1,17  Gerasimos Aravantinos^1,17 

[1] 1st Department of Medical Oncology, "Metropolitan" Hospital, Athens, Greece;1st Propaedeutic Department of Surgery, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;2nd Department of Medical Oncology, "Metropolitan" Hospital, Athens, Greece;2nd Propaedeutic Department of Internal Medicine, Oncology Section, University General Hospital "Attikon", Athens, Greece;424 Army General Hospital, Thessaloniki, Greece;Department of Biostatistics, Hellenic Cooperative Oncology Group Data Office, Athens, Greece;Department of Clinical Therapeutics, "Alexandra" Hospital, University of Athens School of Medicine, Athens, Greece;Department of Medical Oncology, IKA Hospital, Thessaloniki, Greece;Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece;Department of Medical Oncology; "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, "Ippokration" Hospital, Athens, Greece;Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece;Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece;Histopathology Department, "Alexandra" Hospital, Athens, Greece;Laboratory of Histology and Embryology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Oncology Department, "Ippokration" Hospital, Athens, Greece;Third Department of Medical Oncology, "Agii Anargiri" Hospital, Athens, Greece;

关键词: Overall Survival;    Irinotecan;    Hazard Rate;    Metastatic Colorectal Cancer;    Adjuvant Setting;   

DOI  :  10.1186/1741-7015-9-10

 received in 2010-11-30, accepted in 2011-01-31,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundColon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer.MethodsThe study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (IV), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 IV bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years.ResultsThe probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms.ConclusionsIrinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12610000148077

【 授权许可】

CC BY   
© Papadimitriou et al; licensee BioMed Central Ltd. 2011