Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors

J Clin Oncol. 2004 May 15;22(10):1934-43. doi: 10.1200/JCO.2004.11.053.

Abstract

Purpose: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs).

Patients and methods: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR.

Results: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC.

Conclusion: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Germinoma / mortality
  • Germinoma / pathology
  • Germinoma / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Male
  • Medical Records
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • New York
  • Retrospective Studies
  • Salvage Therapy
  • Survival Analysis
  • Thiotepa / administration & dosage*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Thiotepa