HIGH DOSE CHEMOTHERAPY FOR REFRACTORY GERM CELL TUMORS

J Clin Oncol. 2011 Mar 28. [Epub ahead of print]

Conventional-Dose Versus High-Dose Chemotherapy As First Salvage Treatment in Male Patients With Metastatic Germ Cell Tumors: Evidence From a Large International Database.

Lorch A, Bascoul-Mollevi C, Kramar A, Einhorn L, Necchi A, Massard C, De Giorgi U, Fléchon A, Margolin K, Lotz JP, Germà-Lluch JR, Powles T, Kollmannsberger C, Beyer J.

University of Giessen and Marburg, Marburg; Vivantes Klinikum Am Urban, Berlin, Germany; Institut Gustave Roussy; Hospital Tenon, Paris; Centre Leon Berard, Lyon; CRLC Val d'Aurelle, Montpellier; Centre Oscar Lambret, Lille, France; Istituto Nazionale dei Tumori, Milan; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; Indiana University, Bloomington, IN; Seattle Cancer Center Alliance, Seattle, WA; Institut Catala d' Oncologia, Barcelona, Spain; St. Bartholomew's Hospital, London, United Kingdom; and University of British Columbia, Vancouver, Canada.

Abstract

PURPOSE Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience progression with first-line treatment. PATIENTS AND METHODS Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables. Results Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups. CONCLUSION This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population.