Résumé
Abstract only 3506 Background: Perioperative FOLFOX4 is the standard chemotherapy (CT) in patients with resectable metastases from colorectal cancer (CRC) (Nordlinger et al, Lancet 2008). To increase curability and reduce the risk of severe neuropathy, we evaluated the sequential administration of a dose-dense oxaliplatin-based regimen followed by an irinotecan-based regimen. Methods: Patients with CRC and initially resectable or resected metastases were randomized between arm A (control): FOLFOX4 (12 cycles; oxaliplatin 85 mg/m²) or arm B (investigational): FOLFOX7 (6 cycles; oxaliplatin 130 mg/m²) followed by FOLFIRI (6 cycles; irinotecan 180 mg/m²). CT was either perioperative or postoperative. Stratification criteria were: perioperative vs. postoperative CT, surgery alone vs. radiofrequency ablation +/- surgery, Blumgart’s prognostic score (0-1 vs. 2-3 vs. 4-5). Only one metastatic site was allowed, but the number of metastases per organ was not limited. The primary endpoint was disease-free survival (DFS). Results: From May 2004 to June 2010, 284 patients were randomized (142 in each arm). Baseline patient characteristics were similar in both arms. Liver was the main metastatic site. There was only one metastasis in 70 (49.3%) patients in arm A and 69 (48.6%) patients in arm B. CT was administered perioperatively in 168 (59.1%) patients, and postoperatively in 116 (40.9%) patients. In case of perioperative CT, R0-R1 resection was achieved in 58/85 (68.2%) patients in arm A and 67/83 (80.7%) patients in arm B. Grade 3 neuropathy occurred in 34 (23.9%) and 28 (20.0%) patients in arm A and B, respectively. Grade 3/4 thrombocytopenia and gastrointestinal toxicities (nausea, vomiting, diarrhea) were more frequent in arm B. Median follow-up was 50.4 months [95% CI: 45.6-54.4]. Median DFS were 22.4 months [95% CI: 17.9-36.2] in arm A and 23.0 months [95% CI: 19.7-35.6] in arm B (HR=0.97 [95% CI: 0.72-1.31]; p=.856). Conclusions: FOLFOX7 followed by FOLFIRI is not superior to the standard FOLFOX4 chemotherapy in patients with resectable metastatic colorectal cancer.