Estudio radomizado de FOLFOX 4 vs. mas quimioterapia (MIROX) en pacientes con cáncer colorrectal metastático, pasibles de cirugía

Este estudio fracasó en agregar al estándar de FOLFOX 4 para pacientes con cáncer colorrectal metastático FOLFOX7 y FOLFIRI en aumentar el tiempo a la progresión y supervivencia. Es otro ejemplo que no siempre más es mejor.

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/m²) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m²) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m²). 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.

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