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Phase I/II Study of Sequential Dose-Intensified Ifosfamide, Cisplatin, and Etoposide Plus Paclitaxel As Induction Chemotherapy for Poor Prognosis Germ Cell Tumors by the German Testicular Cancer Study Group

Jörg T. Hartmann, Thomas Gauler, Bernd Metzner, Arthur Gerl, Jochen Casper, Oliver Rick, Marius Horger, Jan Schleicher, Günter Derigs, Regine Mayer-Steinacker, Jörg Beyer, Markus A. Kuczyk, Carsten Bokemeyer

From the Departments of Oncology and Hematology and Urology, South West German Comprehensive Cancer Center, University of Tuebingen, Tuebingen; Department of Oncology, West German Cancer Center, Essen; Department of Oncology/Hematology, Klinikum Oldenburg, Oldenburg; Department of Hematology and Oncology, University Hospital Grosshadern, Munich; Department of Hematology and Oncology, University of Rostock, Rostock; Department of Hematology/Oncology, Charite Berlin, Berlin; Department of Oncology, Katharinenhospital Stuttgart, Stuttgart; Department of Hematology and Oncology, University of Mainz, Mainz; Department of Hematology and Oncology, University of Ulm, Ulm; Department of Hematology and Oncology, University of Marburg, Marburg; and Department of Oncology and Hematology, University of Hamburg, Hamburg, Germany

Address reprint requests to Jörg T. Hartmann, MD, PhD, Department of Medical Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, South West German Comprehensive Cancer Center, Eberhard-Karls-University of Tuebingen, Otfried-Mueller-Str 10, 72076 Tuebingen, Germany; e-mail: joerg.hartmann{at}med.uni-tuebingen.de

Purpose To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood–derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features.

Patients and Methods Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m², ifosfamide 10,000 mg/m², and cisplatin 100 mg/m²; cumulative dose; days –6 through –2 per cycle) at three dose levels (135, 175, and 225 mg/m²) applied on day –6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC.

Results Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/µL and thrombocytes less than 25,000/µL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively.

Conclusion Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m² in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.

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

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