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, randomised phase 3 trial
Mené en France sur 284 patients atteints d'un cancer colorectal présentant des métastases résécables, cet essai randomisé multicentrique de phase III compare l'efficacité, du point de vue de la survie sans maladie à 2 ans, et la toxicité de 2 schémas de chimiothérapie, par FOLFOX4 ou par FOLFOX7 puis FOLFIRI
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 3 trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m²) or six cycles of FOLFOX7 (oxaliplatin 130 mg/m²) followed by six cycles of FOLFIRI (irinotecan 180 mg/m²). Randomisation 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 endpoint was 2-year disease-free survival (DFS). Results : 284 patients were randomised, 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. 2-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 (HR=2·15) and synchronous metastases (HR=1·63) were independent prognostic factors for shorter DFS. 5-year overall survival 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. 5-year overall survival 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.
Annals of Oncology 2014