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.
Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer
