Biweekly paclitaxel and cisplatin: a phase I/II study in the first-line treatment of metastatic breast cancer.

An ongoing phase I/II trial in patients with chemotherapy-naive metastatic breast cancer (one adjuvant chemotherapy regimen is allowed) uses a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 90 mg/m2 followed by a 3-hour infusion of cisplatin 60 mg/m2 every 2 weeks given with standard premedications. The protocol called for the escalation of paclitaxel in 10 mg/m2 increments to as much as 130 mg/m2 combined with a fixed 60 mg/m2 cisplatin dose without granulocyte colony-stimulating support in the phase I portion of the trial, but dose-limiting neutropenia identified the initial 90 mg/m2 paclitaxel dose as the maximum tolerated in this biweekly schedule. The phase II portion is continuing to accrue patients and results are preliminary. Twenty-two patients have been enrolled thus far. Of the 16 evaluable for response, four (25%) have had a complete and II (69%) a partial response, for an overall response rate of 94%. Eighteen patients are evaluable for toxicity. Significant neutropenia has been dose limiting, but the mean duration of the absolute neutrophil nadir (< 0.5 x 10(9)/L) is only 2 days. Nonhematologic toxicity has been generally mild, with no grade 4 and few grade 3 toxicities occurring. Nausea, most likely attributable to cisplatin, has occurred frequently, as have mild hypersensitivity reactions. Other nonhematologic toxicity (arthralgias, fatigue, neurologic symptoms) also has been mild.