High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma

Neuro Oncol. 2010 Mar;12(3):297-303. doi: 10.1093/neuonc/nop031. Epub 2010 Jan 11.

Abstract

Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0-M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m(2)/day) on days -8 to -6, and thiotepa (300 mg/m(2)/day) and etoposide (250 mg/m(2)/day) on days -5 to -3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6-44.7 years (median 13.8 years) at ASCR, were treated. Three (12%) died of treatment-related toxicities within 30 days of ASCR, due to multiorgan system failure (n = 2) and aspergillus infection with veno-occlusive disease (n = 1). Tumor recurred in 16 at a median of 8.5 months (range 2.3-58.5 months). Six are event-free survivors at a median of 151.2 months post-ASCR (range 127.2-201.6 months). The Kaplan-Meier estimate of median overall survival is 26.8 months (95% CI: 11.9-51.1 months) and of event-free survival (EFS) and overall survival are both 24% (95% CI: 9.8%-41.7%) at 10 years post-ASCR. M-0 (vs M-1 + ) recurrence prior to protocol, lack of tissue confirmation of relapse, and initial therapy of radiation therapy (RT) alone (vs RT + chemotherapy) were not significantly associated with better EFS (P = .33, .34, and .27, respectively). Trends toward better EFS were noted in patients (n = 5) who received additional RT as part of their retrieval therapy (P = .07) and whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09). This retrieval strategy provides long-term EFS for some patients with previously irradiated recurrent medulloblastoma. The use of additional RT may be associated with better outcome.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medulloblastoma / mortality
  • Medulloblastoma / therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy*
  • Quality of Life
  • Radiotherapy
  • Salvage Therapy / methods*
  • Thiotepa / administration & dosage
  • Young Adult

Substances

  • Etoposide
  • Thiotepa
  • Carboplatin