Résumé
Abstract only 3542 Background: The goal of the study was to test whether adding Irinotecan to a 5-FU/LV adjuvant regimen improves disease free survival (DFS) or overall survival (OS) in optimally resected stages II-III rectal cancers. Primary end-point was DFS. Methods: Six hundred patients were planned to be randomized between 5-FU/LV (control arm) or 5-FU/LV + irinotecan (experimental arm). As only 357 patients had been included from 03/1999 to 12/2005 (178 in control and 179 in experimental arm), the IDMC recommended to close accrual. The trial was stratified by control arm: Mayo-Clinic regimen (A: LV 20 mg/m², 5-FU 425 mg/m² bolus days (d) 1- 5 reapeted at d29,57,92,127 and 162) or LV5-FU2 regimen (A’: LV 200 mg/m², 5-FU 400 mg/m² bolus and 5-FU 600 mg/m² 22-hours infusion d1-2, q 2 w for 12 cycles). The experimental arm (B) was LV5-FU2 + irinotecan 180 mg/m² d1. Results: All 357 randomized patients were evaluable for efficacy. Patient characteristics were well balanced (median age 62 years, stage II 31 %, stage III 69 %, N0 31 %, 68 % received preoperative radiotherapy, and 80 % had sphincter conservation). With follow-up of 156 months, DFS and OS are not statistically increase (81vs 92 events for DFS in experimental and control arm, hazard ratio (HR)=0.805, p=0.154;63 vs 72 events for OS, HR=0.874, p=0.433). Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5FU2 control (33 % vs 16 %, p=0.03), but not when compared with the Mayo Clinic arm (32% vs 36%, p=0.84). Grade 3-4 diarrhea tend to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction p=0.44). Conclusions: In patients with resected stage II-III rectal cancer, adding irinotecan to 5FU/LV led to a non significant increase of DFS and OS. The analysis was planned to have a 60 % power to detect a significant difference with 220 events. With a long term follow up of 8 years only 173 events were observed in our trial. Lack of power and good patient prognosis (thirty one percent of node negative patients) may have impacted the results.