A phase II trial of gemcitabine/carboplatin with or without trastuzumab in the first-line treatment of patients with metastatic breast cancer.

Abstract Purpose The purpose of this study was to evaluate the efficacy and toxicity of the combination of gemcitabine and carboplatin (and with trastuzumab in patients with HER2-positive disease) as first-line treatment for patients with metastatic breast cancer (MBC). Patients and Methods Seventy-four patients who had received no previous chemotherapy for MBC were enrolled. Patients with HER2-negative breast cancer received treatment with gemcitabine 1000 mg/m 2 intravenously (I.V.) on days 1 and 8 and carboplatin area under the curve (AUC) 5 I.V. on day 1. Cycles were repeated every 21 days. Patients with HER2-positive disease also received trastuzumab 8-mg/kg I.V. loading dose, then 6 mg/kg I.V. every 21 days. After the first 29 patients were treated, the carboplatin dose was lowered to AUC 4. Patients were re-evaluated every 6 weeks; responses were measured using Response Evaluation Criteria in Solid Tumors criteria. Results In patients with HER2-negative disease, gemcitabine/carboplatin produced a 34% major response rate; an additional 28% of patients had stable disease ≥ 6 months (overall disease control rate, 62%). Gemcitabine/carboplatin/trastuzumab produced an overall response rate of 66%, with a disease control rate of 77%. Grade 3/4 myelosuppression was common, even after reduction of the carboplatin dose. Only 3 patients treated with the lower dose regimen developed neutropenia and fever, but platelet and red blood cell transfusions were necessary in 24% and 40% of patients, respectively. Trastuzumab did not add to hematologic toxicity. Severe nonhematologic toxicity was uncommon. Conclusion Gemcitabine/carboplatin and gemcitabine/carboplatin/trastuzumab are active first-line regimens for patients with MBC. The gemcitabine/carboplatin combination causes more grade 3/4 myelosuppression than other standard combination regimens for MBC; however, severe nonhematologic toxicity is minimal.