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 studyReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

BMC Medicine

, 9:10

First Online: 31 January 2011Received: 30 November 2010Accepted: 31 January 2011DOI: 10.1186-1741-7015-9-10

Cite this article as: Papadimitriou, C.A., Papakostas, P., Karina, M. et al. BMC Med 2011 9: 10. doi:10.1186-1741-7015-9-10

Abstract

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-m intravenously IV, LV 200 mg-m and 5FU 450 mg-m bolus Arm A versus LV 200 mg-m and 5FU 500 mg-m 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

AbbreviationsALTalanine transaminase

ASTaspartate aminotransferase

CAcancer antigen

CBCcomplete blood cell

CEAcarcinoembryonic antigen

CNScentral nervous system

CPT-11irinotecan

CT scancomputed tomography

DFSdisease-free survival

ECGelectrocardiogram

FOLFIRI5fluorouracil leucovorin and irinotecan

FOLFOX5fluorouracil leucovorin and oxaliplatin

5FU5-fluorouracil

HRhazard rate

IFL regimenirinotecan 5fluorouracil and leucovorin

IVintravenously

G-CSFGranulocyte colony-stimulating factor

LVleucovorin

MMRmismatch repair

OSoverall survival

WHOworld health organization

Electronic supplementary materialThe online version of this article doi:10.1186-1741-7015-9-10 contains supplementary material, which is available to authorized users.

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Author: Christos A Papadimitriou - Pavlos Papakostas - Maria Karina - Lia Malettou - Meletios A Dimopoulos - George Pentheroudakis

Source: https://link.springer.com/







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