Phase I Study of Triweekly Nab-Paclitaxel Combined with S-1 in Patients with HER2-negative Metastatic Breast Cancer

Abstract

Aim: We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC).

Patients and methods: This study was carried out with a 3+3 dose escalation design; patients with HER2-negative MBC received nab-paclitaxel at 180-260 mg/m² on day 1 and S-1 at 65-80 mg/m² daily on days 1-14, repeated every 3 weeks.

Results: The MTD was level 3 (260 mg/m² nab-paclitaxel with 80 mg/m² S-1) and the RD was level 2 (260 mg/m² nab-paclitaxel with 65 mg/m² S-1). Dose-limiting toxicity was observed in two patients at level 3, who had grade 4 neutropenia and grade 3 myalgia, respectively.

Conclusion: The response rate was 66.7%. The clinical benefit rate was 77.8%. Our study shows the efficacy and the feasibility of this combination therapy.

Keywords: Breast cancer; HER2-negative; Nab-paclitaxel; S-1; metastatic; phase I study.