Open Access Research article

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

Christos A Papadimitriou1*, Pavlos Papakostas2, Maria Karina3, Lia Malettou4, Meletios A Dimopoulos1, George Pentheroudakis5, Epaminontas Samantas6, Aristotelis Bamias1, Dimosthenis Miliaras7, George Basdanis8, Nikolaos Xiros9, George Klouvas10, Dimitrios Bafaloukos11, Georgia Kafiri12, Irene Papaspirou13, Dimitrios Pectasides9, Charisios Karanikiotis14, Theofanis Economopoulos9, Ioannis Efstratiou15, Ippokratis Korantzis3, Nikolaos Pisanidis16, Thomas Makatsoris17, Fotini Matsiakou2, Gerasimos Aravantinos6, Haralabos P Kalofonos17 and George Fountzilas3

Author Affiliations

1 Department of Clinical Therapeutics, "Alexandra" Hospital, University of Athens School of Medicine, Athens, Greece

2 Oncology Department, "Ippokration" Hospital, Athens, Greece

3 Department of Medical Oncology; "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

4 Department of Biostatistics, Hellenic Cooperative Oncology Group Data Office, Athens, Greece

5 Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

6 Third Department of Medical Oncology, "Agii Anargiri" Hospital, Athens, Greece

7 Laboratory of Histology and Embryology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

8 1st Propaedeutic Department of Surgery, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

9 2nd Propaedeutic Department of Internal Medicine, Oncology Section, University General Hospital "Attikon", Athens, Greece

10 2nd Department of Medical Oncology, "Metropolitan" Hospital, Athens, Greece

11 1st Department of Medical Oncology, "Metropolitan" Hospital, Athens, Greece

12 Department of Pathology, "Ippokration" Hospital, Athens, Greece

13 Histopathology Department, "Alexandra" Hospital, Athens, Greece

14 424 Army General Hospital, Thessaloniki, Greece

15 Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece

16 Department of Medical Oncology, IKA Hospital, Thessaloniki, Greece

17 Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece

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BMC Medicine 2011, 9:10  doi:10.1186/1741-7015-9-10

Published: 31 January 2011

Abstract

Background

Colon 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.

Methods

The 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.

Results

The 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.

Conclusions

Irinotecan 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 registration

Australian New Zealand Clinical Trials Registry: ACTRN12610000148077