Phase I study of S-1 in combination with trastuzumab for HER2-positive metastatic breast cancer.

BACKGROUND As there are no reports of S-1 in combination with trastuzumab in clinical settings, we evaluated the safety and efficacy of S-1 in combination with trastuzumab for human epidermal-growth factor receptor (HER2)-positive metastatic breast cancer (MBC) and determined the recommended dose (RD). PATIENTS AND METHODS Patients with HER2-positive MBC received trastuzumab (a fixed initial dose of 4 mg/kg/day, then 2 mg/kg every week) plus S-1 (4 weeks followed by a 2-week rest) every 42 days. The dosage of S-1 was set of three levels (1: 80 mg/m², 2: 65 mg/m², 3: 50 mg/m²). The purposes of this study were the determination of the RD and safety. Dose-limiting toxicity (DLT) data were continually monitored to assess S-1 dose decreases. RESULTS Twelve patients were treated at level 1. Because no patients experienced DLT, the RD of S-1 plus trastuzumab therapy was 80 mg/m² S-1 and 4 mg/kg followed by 2 mg/kg trastuzumab. The overall response rate and disease control rate were 33.3% and 83.3%, respectively. CONCLUSION S-1 plus trastuzumab could be safely and effectively used for the treatment of HER2-positive MBC. The RD for a phase II study of this regimen was determined to be 80 mg/m² S-1 and 2 mg/kg trastuzumab every week (loading dose, 4 mg/kg).