Paclitaxel in salvage therapy for germ cell tumors.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a single agent showed antitumor activity in patients with germ cell tumors resistant to combination cisplatin-containing chemotherapy and has been included in two risk-directed first-line combination salvage programs. Patients with relapsed germ cell tumors originating from a testis primary site were treated in a phase I/II trial of conventional-dose paclitaxel (given at 175, 215, and 250 mg/m2 dose levels), ifosfamide, plus cisplatin. Ten (63%) of 16 assessable patients achieved a complete response, eight (50%) of which remain durable at a median follow-up of 16 months. The 250 mg/m2 dose of paclitaxel was chosen for the phase II trial and accrual continues. In a second trial, patients with cisplatin-resistant germ cell tumors and unfavorable prognostic features (previous incomplete response to first-line chemotherapy or an extragonadal primary site) were treated with a dose-intensive program consisting of rapid recycling of paclitaxel plus ifosfamide followed by carboplatin plus etoposide with stem cell support. The target carboplatin dose was based on the Calvert formula and escalated from an area under the concentration-time curve of 12 to 32 mg/mL min among patient cohorts. Ten (56%) of 18 assessable patients achieved a complete response, and seven (39%) remain in complete response at a median follow-up of 11 months. Hematologic toxicity was moderately severe, but no treatment-related deaths have occurred. Accrual to the trial continues, and pharmacology studies for carboplatin are being correlated with the target area under the concentration-time curve by the Calvert formula.