Carboplatin in the treatment of advanced breast cancer: a phase II study using a pharmacokinetically guided dose schedule.

PURPOSE: We performed a phase II study of single-agent carboplatin against metastatic/locally advanced breast cancer using a pharmacokinetically guided dose schedule, to define further the potential role for this agent in combination and high-dose therapy. PATIENTS AND METHODS: Forty patients with metastatic/locally advanced breast cancer were treated with carboplatin based on glomerular filtration rate (GFR) to achieve an area under the concentration-versus-time curve (AUC) of 7 mg/mL.min, with each course repeated at 4-week intervals. The median age was 57 years (range, 37 to 71). RESULTS: Ten patients achieved a partial response (PR), for an overall response rate of 25% (95% confidence interval, 13% to 41%). One of 13 (8%) previously treated patients responded compared with nine of 27 (33%) patients who had not received previous chemotherapy. Median response duration was 18 weeks (range, 10 to 68). World Health Organization (WHO) grade 2 or greater toxicity was as follows: anemia, 42%; leukopenia, 20%; thrombocytopenia, 35%; nausea/vomiting, 39%; and infection, 9%. CONCLUSION: This study confirms other reports indicating that carboplatin has moderate activity in previously untreated patients, but not in previously treated patients. In our view, carboplatin is a more appropriate agent than cisplatin for inclusion in high-dose chemotherapy schedules with autologous bone marrow rescue, and our results support the concept of calculating dose escalation on the basis of the area under the dose-response curve using the Calvert formula, rather than on surface area.