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.
Ann Oncol
; 26(2): 340-7, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25403578
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Camptotecina
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Neoplasias Colorrectales
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Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article