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Journal of Clinical Oncology, Vol 18, Issue 6 (March), 2000: 1173-1180
© 2000 American Society for Clinical Oncology

Sequential Dose-Intensive Paclitaxel, Ifosfamide, Carboplatin, and Etoposide Salvage Therapy for Germ Cell Tumor Patients

By Robert J. Motzer, Madhu Mazumdar, Joel Sheinfeld, Dean F. Bajorin, Homer A. Macapinlac, Manjit Bains, Lilian Reich, Carlos Flombaum, Tania Mariani, William P. Tong, George J. Bosl

From the Genitourinary Oncology, Nuclear Medicine, and Renal Services; Divisions of Solid Tumor Oncology, Thoracic Surgery, and Hematologic Oncology; and Departments of Medicine, Epidemiology and Biostatistics, Therapeutic Pharmacology, Urology, Surgery, and Radiology, Memorial Sloan-Kettering Cancer Center; and the Department of Medicine, Cornell University Medical College, New York, NY.

Address reprint requests to Robert J. Motzer, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email motzerr{at}mskcc.org

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood–derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison.

PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m2 plus ifosfamide 6 g/m2 were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1,200 mg/m2, 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 AUC.

RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; 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 support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.


Related Correspondence

  • Ototoxicity in Patients With Dose-Intensive Therapy for Cisplatin-Resistant Germ Cell Tumors
    Adrian Dubs, Emanuel Jacky, Rolf Stahel, Christian Taverna, and Hanspeter Honegger
    JCO 2004 22: 1158 [Full Text]

Related Reply

  • In Reply:
    Robert J. Motzer
    JCO 2004 22: 1158-1159 [Full Text]


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