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Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide in Previously Treated Germ Cell Tumors

G. Varuni Kondagunta, Jennifer Bacik, Joel Sheinfeld, Dean Bajorin, Manjit Bains, Lillian Reich, John Deluca, Amy Budnick, Nicole Ishill, Madhu Mazumdar, George J. Bosl, Robert J. Motzer

From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine; Departments of Epidemiology and Biostatistics, Urology, Surgery, and Audiology, and Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center; and Department of Medicine, Joan and Sanford I. Weill Medical College of Cornell University Medical College, New York, NY

Address reprint requests to G. Varuni Kondagunta, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: kondaguv{at}mskcc.org

Purpose: To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential, dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely to experience treatment failure with conventional-dose salvage treatment. This prospective trial followed a similarly designed report of TICE, which used a different means of carboplatin dosing.

Patients and Methods: The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis, followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC.

Results: Twenty-three (49%) of 47 assessable patients achieved a complete response (CR) to chemotherapy. An additional three patients (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients experienced relapse, but 24 patients (51%) are alive and free of disease at a median follow-up time of 40 months. Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection. When combined with results of the prior trial of similar design, TICE chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive with no evidence of disease.

Conclusion: TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy.

Supported by Grants No. CA 05826 and NIH K24 CA82431 from the National Cancer Institute and by the Craig D. Tifford Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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