FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial
M Hebbar, B Chibaudel, T André, L Mineur, D Smith, C Louvet, J L Dutel, M Ychou, J L Legoux, M Mabro, R Faroux, D Auby, D Brusquant, A Khalil, S Truant, A Hadengue, C Dalban, B Gayet, F Paye, F R Pruvot, F Bonnetain, B Landi, M Flesch, E Carola, P Martin, E Vaillant, A de Gramont, Group Coopérateur Multidisciplinaire en Oncologie (GERCOR) Group, M Hebbar, B Chibaudel, T André, L Mineur, D Smith, C Louvet, J L Dutel, M Ychou, J L Legoux, M Mabro, R Faroux, D Auby, D Brusquant, A Khalil, S Truant, A Hadengue, C Dalban, B Gayet, F Paye, F R Pruvot, F Bonnetain, B Landi, M Flesch, E Carola, P Martin, E Vaillant, A de Gramont, Group Coopérateur Multidisciplinaire en Oncologie (GERCOR) Group
Abstract
Background: Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative.
Patients and methods: In this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m(2)) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m(2)) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m(2)). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong's prognostic score. The primary end point was 2-year disease-free survival (DFS).
Results: A total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7-FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7-FOLFIRI.
Conclusions: FOLFOX7-FOLFIRI is not superior to FOLFOX4 in patients with resectable metastatic CRC. Five-year OS rates observed in both groups are the highest ever reported in this setting, possibly reflecting the pragmatic approach to chemotherapy timing.
Clinical trials number: NCT00268398.
Keywords: chemotherapy; colorectal cancer; irinotecan; metastases; oxaliplatin; resection.
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Source: PubMed