High-dose chemotherapy as primary treatment for poor-risk germ-cell tumors: the Memorial Sloan-Kettering experience (1988-1999)

Int J Cancer. 1999 Dec 10;83(6):834-8. doi: 10.1002/(sici)1097-0215(19991210)83:6<834::aid-ijc25>3.0.co;2-i.

Abstract

Although the majority of patients with poor-risk germ-cell tumors (GCTs) will achieve a durable complete remission (CR) with standard first-line therapy, 20% to 30% of them will either relapse or fail to achieve an initial CR and eventually die. For this reason, the strategy of using high-dose (HD) chemotherapy with autologous stem-cell support has been investigated to improve the chances of cure attainable in the salvage setting, but at a cost of significant morbidity and mortality. Treatment using HD therapy in the first-line setting offers the promise of reducing morbidity and mortality while increasing efficacy. At Memorial Sloan-Kettering Cancer Center (MSKCC), trials were conducted to test this hypothesis. Patients at high risk of relapse following conventional therapy were identified, based on post-treatment serum marker concentrations that failed to appropriately decline by predicted half-life after several cycles of standard treatment. These patients received first-line HD treatment. Patients received a 2-drug HD regimen in one trial and an intensified 3-drug regimen in another, each with autologous bone marrow transplantation. These patients had improved overall and event-free survival rates (p = 0.001 and 0.003, respectively) compared with historical controls who underwent standard first-line treatment, with a lower incidence of treatment-related mortality than patients who received HD therapy in the salvage setting. Randomized trials are under way to prospectively verify these results.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bone Marrow Transplantation*
  • Cancer Care Facilities
  • Carboplatin / administration & dosage
  • Cisplatin / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Dactinomycin / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Germinoma / drug therapy*
  • Germinoma / mortality
  • Germinoma / therapy*
  • Humans
  • Male
  • New York City
  • Retrospective Studies
  • Salvage Therapy
  • Survival Rate
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / therapy*
  • Transplantation, Autologous
  • Vinblastine / administration & dosage

Substances

  • Bleomycin
  • Dactinomycin
  • Vinblastine
  • Etoposide
  • Cyclophosphamide
  • Carboplatin
  • Cisplatin

Supplementary concepts

  • CEC protocol
  • VAB-6 regimen