Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database

J Clin Oncol. 2011 Jun 1;29(16):2178-84. doi: 10.1200/JCO.2010.32.6678. Epub 2011 Mar 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cisplatin / administration & dosage
  • Databases, Factual
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage
  • Humans
  • Ifosfamide / administration & dosage
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Paclitaxel / administration & dosage
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Salvage Therapy / methods*
  • Thiotepa / administration & dosage
  • Vinblastine / administration & dosage
  • Young Adult

Substances

  • Vinblastine
  • Etoposide
  • Thiotepa
  • Carboplatin
  • Paclitaxel
  • Cisplatin
  • Ifosfamide