Interim results of a phase I/II study of biweekly paclitaxel and cisplatin in patients with metastatic breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered in a 3-hour infusion exhibits both a rapid decline to, and recovery from, the hematologic nadir. This suggests that a biweekly administration schedule of this agent either alone or in combination with agents that have limited hematologic toxicity may be possible. The objective of this study was to determine the tolerability and activity of biweekly administered paclitaxel in combination with cisplatin in patients with metastatic breast cancer. Patients with metastatic breast cancer who may have received up to one prior chemotherapy regimen in the adjuvant setting were eligible. Paclitaxel was administered intravenously by a 3-hour infusion followed by intravenous cisplatin every 2 weeks in the ambulatory setting. Twenty-nine patients have been entered in the study, of whom 27 had received prior adjuvant chemotherapy. Dose-limiting toxicity for the phase I study proved to be failure to recover the neutrophil count to more than 750 cells/microL by day 15; the maximum tolerated dose was therefore paclitaxel 90 mg/m2 and cisplatin 60 mg/m2 every 2 weeks. Nonhematologic toxicities were mild and included fatigue, arthralgias, peripheral neuropathy, and nausea and vomiting. At the present analysis, 234 cycles of treatment have been given. Among 27 patients evaluable for response (four of whom are still receiving therapy), three have had complete remissions and 18 partial responses, for an interim overall response rate of 78%. In summary, weekly paclitaxel and cisplatin is a safe and active combination in the treatment of metastatic breast cancer. Final determination of toxicity and activity will be published at the conclusion of this study.