High efficacy of gemcitabine and cisplatin plus trastuzumab in patients with HER2-overexpressing metastatic breast cancer: a phase II study.

摘要

AIMS: Effective and tolerable regimens are sought specifically in women who have been pre-treated with anthracyclines and taxanes. Gemcitabine and cisplatin plus trastuzumab has shown synergistic activity in vitro, and provides a new mechanism of drug interaction. This multicentre phase II study aimed to evaluate the efficacy and tolerability of gemcitabine and cisplatin plus trastuzumab in previously treated patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: Previously treated patients with human epidermal growth factor receptor 2 (HER2) overexpressing MBC were enrolled in a multicentre phase II study (DAKO Hercep Test 3+). Treatment consisted of gemcitabine (750 mg/m2), cisplatin (30 mg/m2) given on days 1 and 8 every 3 weeks, and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly). RESULTS: Twenty patients were recruited, all of whom had previously received chemotherapy (12 pre-treated with taxanes, 18 pre-treated with anthracyclines seven pre-treated with taxanes and trastuzumab). A median of six cycles of the study treatment was delivered. There were eight partial responses, for an overall response rate of 40% (95% confidence interval 16.5-63.5%). The clinical benefit rate (complete response plus partial response plus stable disease) was 80% (95% CI 54.2-95.8%). The response rate in patients who had already received a trastuzumab-based regimen for MBC was 57.1% (95% CI 7.7-100%). Median time to progression was 10.2 months, and median overall survival was 18.8 months. Main toxicities were leukopenia (grade 3 in 55% of patients) and thrombocytopenia (grade 3 in 35% and grade 4 in 5% of patients). Non-haematological toxicity was rarely severe. CONCLUSIONS: Combination chemotherapy with gemcitabine and cisplatin plus trastuzumab is well tolerated and active in patients with HER2 overexpressing MBC, even after prior exposure to anthracyclines and taxanes.