Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer

Abstract

Purpose: To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer.

Patients and methods: This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m² on day 1 and S-1 at 65-80 mg/m² daily on days 1 to 14.

Results: Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m² nab-PTX with 80 mg/m² S-1). The recommended dose determined was level 3 (220 mg/m² nab-PTX with 80 mg/m² S-1). The response rate was 60.0%. The disease control rate was 70.0%.

Conclusion: This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.

Keywords: Combination therapy; HER2-negative metastatic breast cancer; Nab-paclitaxel; Phase I study; S-1.