Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients

Purpose: To evaluate the efficacy and toxicity of sequential, dose-intensif ied chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide admin istered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in re sponse to conventional-dose salvage programs. Carboplatin was dose escalate d by target area under the curve (AUC; in [milligrams per milliliter] x min utes) among patient cohorts, and pharmacokinetic studies were performed for comparison. Patients and Methods: Thirty-seven previously treated patients who had cisp latin-resistant GCT and unfavorable prognostic features for response to con ventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 m g/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis , followed by three cycles of carboplatin plus etoposide given 14 to 21 day s apart with reinfusion of PBSCs. The dose of etoposide war 1,200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUG. Results: Twenty-one patients (57%) achieved a complete response and an addi tional two patients (5%) achieved a partial response with normal tumor mark ers; therefore, 23 (62%) achieved a favorable response. Eight patients rela psed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of car boplatin/etoposide cycles were associated with hospitalization for nadir fe ver. The AUC of carboplatin measured in serum was lower than the target AUG ; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. Conclusion: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC s upport was relatively well tolerated. The durable complete response proport ion was substantial in patients with unfavorable prognostic features for ac hieving durable complete response to conventional-dose salvage programs. Op timal dosing of carboplatin in the high-dose setting warrants further inves tigation. (C) 2000 by American Society of Clinical Oncology.