Oxaliplatin plus high-dose leucovorin and 5-fluorouracil in pretreated advanced breast cancer: a phase II study.

Background: The purpose of this study was to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.

Patients And Methods: Fifty anthracycline- and taxane-pretreated MBC patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2)/day as a 2-h infusion followed by bolus 5-FU 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles.

Results: The median age was 51 years (range 34-75). Twenty patients (40%) had received three or more chemotherapeutic regimens, 64% had three or four metastatic sites and 78% had visceral metastases. All patients had prior exposure to anthracyclines and taxanes. Based on an intention-to-treat analysis, one patient (2%) achieved a complete response and 16 (32%) a partial response, for a 34% overall response rate. Twenty-one patients (42%) had stable disease and 12 (24%) progressive disease. The median time to tumor progression was 5.3 months (range 0.5-12.8) and the median overall survival was 12.3 months (range 0.5-19.2). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 32% and 18%, respectively. Febrile neutropenia was experienced by three patients (6%), who were successfully treated. Grade 3/4 neurotoxicity was reported in 14% of the patients and gradually declined after treatment discontinuation. Cycle delays were reported in 28% of patients and dose reductions in 26%. Alopecia, nausea-vomiting, diarrhea and mucositis were not significant. There were no treatment-related deaths.

Conclusion: The combination of oxaliplatin plus 5-FU/LV seems to be an active regimen in patients with MBC and prior exposure to anthracyclines and taxanes with a good safety profile. The incidence of severe toxicity was quite low and the compliance of patients to the treatment was satisfactory. The results obtained with this regimen could be considered encouraging in this heavily pretreated group of breast cancer patients with a high incidence of visceral metastases.