Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma.

To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas.
From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue.
Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively.
This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.
AuthorsSusan N Chi, Sharon L Gardner, Adam S Levy, Edmond A Knopp, Douglas C Miller, Jeffrey H Wisoff, Howard L Weiner, Jonathan L Finlay
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 24 Pg. 4881-7 (Dec 15 2004) ISSN: 0732-183X [Print] United States
PMID15611503 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Mesna
  • Cisplatin
  • Leucovorin
  • Methotrexate
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Cerebellar Neoplasms (drug therapy, pathology, surgery)
  • Child
  • Child, Preschool
  • Cisplatin (administration & dosage, adverse effects)
  • Cyclophosphamide (administration & dosage, adverse effects)
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Etoposide (administration & dosage, adverse effects)
  • Female
  • Humans
  • Leucovorin (administration & dosage)
  • Male
  • Medulloblastoma (drug therapy, pathology, surgery)
  • Mesna (administration & dosage)
  • Methotrexate (administration & dosage, adverse effects)
  • Risk Factors
  • Stem Cell Transplantation
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine (administration & dosage, adverse effects)

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