Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed children

Med Pediatr Oncol. 2002 Sep;39(3):168-74. doi: 10.1002/mpo.10137.

Abstract

Background: Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors.

Procedure: Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m(2) and etoposide 100 mg/m(2) on Days 1 & 2, and methotrexate 8 g/m(2) on Day 3, repeated at 21-28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference.

Results: The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged < 3 years at diagnosis had a combined PR and CR rate of 71% compared to 81% in patients aged > 3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common.

Conclusions: The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Infant
  • Male
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / pathology
  • Methotrexate / administration & dosage
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Prognosis
  • Treatment Outcome

Substances

  • Etoposide
  • Carboplatin
  • Methotrexate