Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer - ScienceDirect

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作者：

Maindrault-Gbel F.，de Gramont A.，C Louvet，T André，E Carola，V Gilles，Lotz J.-P.，C Tournigand，M Mabro，Molitor J.-L.

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摘要：

Background studies of bimonthly 48-hour regimens of high-dose leucovorin (LV) (FOLinic acid), 5-fluorouracil (5-FU) by continuous infusion combined with OXaliplatin (FOLFOX) in pretreated patients with metastatic colorectal cancer suggest that oxaliplatin dose intensity is an important prognostic factor for response rate and progression-free survival (PFS). To help define the optimal dose schedule for oxaliplatin in pretreated metastatic colorectal cancer, we retrospectively analyzed data from three phase II studies using different FOLFOX regimens (FOLFOX2, 3 and 6). Patients and methods Data on 126/161 patients were analyzed. FOLFOX2 included oxaliplatin 100 mg/m2 FOLFOX3, 85 mg/m2 and FOLFOX6, 100 mg/m2 (added to a simplified LV-5-FU regimen), all as two-hour infusions. A total of 47 patients received low dose intensity oxaliplatin (LDI:≤85 mg/m2/2 weeks) and 79 patients high dose intensity oxaliplatin (HDI:>85 mg/m2/2 weeks). Results Objective responses occurred in 31 (39%) HDI patients and 9 (19%) LDI patients (P=0.03). Median PFS was 28 weeks, with 52% of HDI patients progression free at 6 months, and 26 weeks with 36% of LDI patients progression free at six months (P=0.02). Increased oxaliplatin dose intensity was not associated with increased neurotoxicity or other toxicities. FOLFOX are among the most effective regimens for treating LV-5-FU-resistant metastatic colorectal cancer. Conclusions This study shows that oxaliplatin dose intensification significantly improves response rate and PFS in pretreated metastatic disease without increasing severe toxicity.

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关键词：

Humans Adenocarcinoma Colorectal Neoplasms Neoplasm Metastasis Gastrointestinal Diseases Nervous System Diseases Neutropenia Organoplatinum Compounds Fluorouracil Leucovorin