Vinorelbine, methotrexate and fluorouracil (VMF) as first-line therapy in metastatic breast cancer: a randomized phase II trial.

Background: The purpose of this study was to determine the best tolerated and efficacious dose of vinorelbine given once or twice in 3-week cycles in combination with methotrexate and fluorouracil (VMF).

Patients And Methods: Vinorelbine 40 mg/m(2) was given as follows: 20 mg/m(2) on days 1 and 8 (group 1); 30 mg/m(2) on day 1 and 10 mg/m(2) on day 8 (group 2); or 40 mg/m(2) on day 1 (not exeeding 60 mg/m(2)) (group 3). The methotrexate dose was 40 mg/m(2) on day 1 and the fluorouracil dose 600 mg/m(2) on days 1 and 8. Thirty patients with evaluable metastases were randomly allocated to the groups (first step). The second step was to exclude the worst tolerated regimen and then to expand the study to 60 patients. Thus, group 1 had 26 patients, group 2 had 24 patients and group 3 had 10 patients.

Results: World Health Organization (WHO) grade 3 hematological toxicity occurred in 23%, 36% and 50% of patients and grade 4 in 39%, 32% and 50% of patients in groups 1, 2 and 3, respectively; grade 3 infections were observed in 15%, 9% and 10% of patients in groups 1, 2 and 3, and grade 4 infections in 5% and 10% of patients in groups 2 and 3, respectively. Nonhematological toxicity included a mild to moderate neurotoxicity manifesting as constipation, abdominal colics and myalgia in the majority of patients. One patient in group 3 had serious convulsions after vinorelbine administration; she also developed neutropenic sepsis; all symptoms were reversible. No patient died from side-effects. The objective response rates were 50%, 55% and 44% for groups 1, 2 and 3, respectively. Median time to progression was 7, 10 and 8 months and median survival time was 26, 23 and 16 months in groups 1, 2 and 3, respectively.

Conclusion: VMF regimens where the vinorelbine dose (40 mg/m(2)) is divided (20 + 20 mg/m(2) and 30 + 10 mg/m(2)) between days 1 and 8 of a 3-week cycle are equally well tolerated and the efficacy is comparable to other modern first line regimens used in the treatment of metastatic breast cancer.