Treatment of early childhood medulloblastoma by postoperative chemotherapy alone

N Engl J Med. 2005 Mar 10;352(10):978-86. doi: 10.1056/NEJMoa042176.

Abstract

Background: The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone.

Methods: After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate. Treatment was terminated if a complete remission was achieved. Leukoencephalopathy and cognitive deficits were evaluated.

Results: Forty-three children were treated according to protocol. In children who had complete resection (17 patients), residual tumor (14), and macroscopic metastases (12), the five-year progression-free and overall survival rates (+/-SE) were 82+/-9 percent and 93+/-6 percent, 50+/-13 percent and 56+/-14 percent, and 33+/-14 percent and 38+/-15 percent, respectively. The rates in 31 patients without macroscopic metastases were 68+/-8 percent and 77+/-8 percent. Desmoplastic histology, metastatic disease, and an age younger than two years were independent prognostic factors for tumor relapse and survival. Treatment strategies at relapse were successful in 8 of 16 patients. There were no major instances of unexpected toxicity. In 19 of 23 children, asymptomatic leukoencephalopathy was detected by magnetic resonance imaging. After treatment, the mean IQ was significantly lower than that of healthy controls within the same age group but higher than that of patients in a previous trial who had received radiotherapy.

Conclusions: Postoperative chemotherapy alone is a promising treatment for medulloblastoma in young children without metastases.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cerebellar Neoplasms / drug therapy*
  • Cerebellar Neoplasms / psychology
  • Cerebellar Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Etoposide / administration & dosage
  • Follow-Up Studies
  • Humans
  • Infant
  • Intelligence / drug effects
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / psychology
  • Medulloblastoma / secondary
  • Medulloblastoma / surgery
  • Methotrexate / administration & dosage
  • Neoplasm Recurrence, Local / drug therapy
  • Neuropsychological Tests
  • Postoperative Care
  • Proportional Hazards Models
  • Remission Induction
  • Survival Analysis
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Carboplatin
  • Methotrexate