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First-Line High-Dose Chemotherapy Compared With Standard-Dose PEB/VIP Chemotherapy in Patients With Advanced Germ Cell Tumors: A Multivariate and Matched-Pair Analysis

From the Department of Hematology/Oncology, University of Tuebingen Medical Center, and Institute for Medical Information Processing, University of Tuebingen, Tuebingen; Department of Internal Medicine, West German Cancer Center, Essen; Department of Hematology/Oncology, Rudolf-Virchow University Clinic, Berlin; Department of Hematology/Oncology, Hannover University Medical School, Hannover; and Department of Hematology/Oncology, University of Halle, Halle, Germany; Department of Hematology/Oncology, Indiana University, Indianapolis, IN; and Division of Hematology/Oncology, Oregon Health Science University, Portland, OR.

Address reprint requests to C. Bokemeyer, MD, Department of Hematology/Oncology, University of Tuebingen Medical Center, Otfried-Mueller-St 10, 72076 Tuebingen, Germany.

PURPOSE: To compare first-line high-dose chemotherapy (HD-CT) with autologous blood stem-cell transplantation to standard-dose chemotherapy (SD-CT) in male patients with advanced germ cell tumors (GCTs), a matched-pair analysis was performed within a homogenous group of patients classified as having either Indiana advanced disease or a poor prognosis according to International Germ Cell Cancer Consensus Group (IGCCCG) criteria.

PATIENTS AND METHODS: A multivariate analysis was performed that included 147 consecutive patients who had received sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) therapy (HD-CT) in a German multicenter trial between 1993 and 1997 and 309 patients who had been treated with standard-dose cisplatin, etoposide, and bleomycin (PEB) or VIP chemotherapy (SD-CT) within two randomized trials at Indiana University between 1984 and 1992.

RESULTS: Multivariate analysis demonstrated HD-CT to be significantly superior to SD-CT when adjustments were made for prognostic factors (P = .021). Primary tumor site (mediastinal v retroperitoneal/gonadal, P = .035) and presence of visceral metastases (P = .0004) were shown to be significant prognostic factors for overall survival. On the basis of these factors, as well as on tumor marker levels (good, intermediate, or poor, according to IGCCCG criteria), 146 of 147 HD-CT patients were fully matched to an SD-CT patient. Median follow-up was 21 months (range, 0 to 70 months) for the HD-CT patients and 22 months (range, 0 to 90 months) for the SD-CT patients. Two-year progression-free survival (75% v 59%) and overall survival (82% v 71%) were significantly prolonged in HD-CT patients (P = .0056 and P = .0184, respectively).

CONCLUSION: The results indicate that first-line HD-CT in patients with poor-prognosis GCT may result in a significant improvement of progression-free and overall survival as compared with SD-CT. Salvage HD-CT seems not to compensate this survival advantage.

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