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

Background: studies of bimonthly 48-hour regimens of high-dose leucovorin ( LV) (FOLinic acid), 5-fluorouracil (5-FU) by continuous infusion combined w ith OXaliplatin (FOLFOX) in pretreated patients with metastatic colorectal cancer suggest that oxaliplatin dose intensity is an important prognostic f actor for response rate and progression-free survival (PFS). To help define the optimal dose schedule for oxaliplatin in pretreated metastatic colorec tal cancer, we retrospectively analyzed data from three phase II studies us ing different FOLFOX regimens (FOLFOX2, 3 and 6). Patients and methods: Data on 126/161 patients were analyzed. FOLFOX2 inclu ded oxaliplatin 100 mg/m(2); FOLFOX3, 85 mg/m(2); and FOLFOX6, 100 mg/m(2) (added to a simplified LV-5-FU regimen), all as two-hour infusions. A total of 47 patients received low dose intensity oxaliplatin (LDI: less than or equal to 85 mg/m(2)/2 weeks) and 79 patients high dose intensity oxaliplati n (HDI: > 85 mg/m(2)/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 progres sion free at six months (P = 0.02). Increased oxaliplatin dose intensity wa s not associated with increased neurotoxicity or other toxicities. FOLFOX a re among the most effective regimens for treating LV-5-FU-resistant metasta tic colorectal cancer. Conclusions: This study shows that oxaliplatin dose intensification signifi cantly improves response rate and PFS in pretreated metastatic disease with out increasing severe toxicity.