UFT plus Oral Folinic Acid with Alternating Oral and Intravenous Vinorelbine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes

Abstract

Background: We retrospectively evaluated the activity and toxicity of uracil/tegafur (UFT) plus oral folinic acid in combination with vinorelbine (alternating intravenous (IV) on day 1 and oral on day 8) in patients with metastatic breast cancer. Patients and Methods: Treatment consisted of IV vinorelbine 25 mg/m² on day 1 and 60 mg/m² orally on day 8, and oral UFT 300 mg/m² plus leucovorin 60 mg/m² on days 1–14 with 21 days interval. All patients were refractory to anthracyclines and taxanes. Results: Partial response (PR) was observed in 3 (9.7%) and stable disease (SD) was observed in 13 (41.9%) patients. Total clinical benefit (PR + SD) of the combination was 51.6%. The median response duration was 3 (range 1–11.8) months. Median overall survival was 9.8 months (95% confidence interval (CI): 7.5–12.1), and median time to progression was 3.4 months (95% CI: 2.3–4.5). The most common toxicities were hematologic, including 4 (12.9%) cases of grade 3 neutropenia and 4 (12.9%) cases of grade 4 neutropenia. Grade 3 diarrhea was reported in 2 (3.2%) patients. 3 (9.7%) patients had hand-foot syndrome. Febrile neutropenia was observed in 1 patient. Conclusions: Although the combination is safe and convenient in clinical practice, it has only moderate activity in metastatic breast cancer patients.

A Phase I Study of UFT-Oral Vinorelbine in Metastatic Breast Cancer

“…Many studies have investigated the UFT/folinic acid and vinorelbine combination, in the search for the best treatment regimen for advanced breast cancer. The most recent publication reported that patients receiving UFT and vinorelbine with the following schedule: intravenous vinorelbine 25 mg/m 2 on day 1 and 60 mg/m 2 orally on day 8, and oral UFT 300 mg/m 2 plus folinic acid 60 mg/m 2 on days 1–14 with a 21-day interval, presented a total clinical benefit of 51.6% [12]. The most common toxicities were hematological, including 12.9% of grade 3 neutropenia and 12.9% of grade 4 neutropenia; 9.7% of the patients had hand-foot syndrome.…”

“…Dose levels were determined based on the results of the previous single-agent and combination chemotherapy trials [11,12,13,14,16,17]. The escalated dose design was based on the Fibonacci ‘3 + 3’ schedule [18].…”

“…It exerts its neoplastic action by preventing tubulin polymerization and arresting mitosis at metaphase. The combination of oral vinorelbine and fluoropyrimidine was previously studied in MBC [11,12,13,14]. As the ultimate goal in MBC management is to prolong the duration of life while maintaining a good quality of life, the choice of UFT and oral vinorelbine combination was particularly attractive.…”