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Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study.

Abstract

PURPOSE
To determine whether preradiotherapy (RT) chemotherapy would improve outcome for Chang stage M0-1 medulloblastoma when compared with RT alone. Chemotherapy comprised vincristine 1.5 mg/m2 weekly for 10 weeks and four cycles of etoposide 100 mg/m2 daily for 3 days, and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.5 g/m2.
PATIENTS AND METHODS
Patients aged 3 to 16 years inclusive were randomly assigned to receive 35 Gy craniospinal RT with a 20 Gy posterior fossa boost, or chemotherapy followed by RT.
RESULTS
Of 217 patients randomly assigned to treatment, 179 were eligible for analysis (chemotherapy + RT, 90 patients; RT alone, 89 patients). Median age was 7.67 years, and median follow-up was 5.40 years. Overall survival (OS) at 3 and 5 years was 79.5% and 70.7%, respectively. Event-free survival (EFS) at 3 and 5 years was 71.6% and 67.0%, respectively. EFS was significantly better for chemotherapy and RT (P =.0366), with EFS of 78.5% at 3 years and 74.2% at 5 years compared with 64.8% at 3 years and 59.8% at 5 years for RT alone. There was no statistically significant difference in 3-year and 5-year OS between the two arms (P =.0928). Multivariate analysis identified use of chemotherapy (P =.0248) and time to complete RT (P =.0100) as having significant effect on EFS.
CONCLUSION
This is the first large multicenter randomized study to demonstrate improved EFS for chemotherapy compared with RT alone. It is anticipated that this regimen could reduce ototoxicity and nephrotoxicity compared with cisplatin-containing schedules. The importance of avoiding interruptions to RT has been confirmed.

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  • Publisher Full Text
  • Authors

    Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Walker DA, Pizer BL, Imeson J, Lashford LS, International Society of Paediatric Oncology, United Kingdom Children's Cancer Study Group

    Institution

    Cookridge Hospital, Leeds, West Yorkshire, LS16 6QB, United Kingdom. Roger.Taylor@Leedsth.nhs.uk

    Source

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 21:8 2003 Apr 15 pg 1581-91

    MeSH

    Adolescent
    Antineoplastic Combined Chemotherapy Protocols
    Carboplatin
    Cerebellar Neoplasms
    Chemotherapy, Adjuvant
    Child
    Child, Preschool
    Cyclophosphamide
    Drug Administration Schedule
    Etoposide
    Female
    Follow-Up Studies
    Great Britain
    Humans
    Male
    Medulloblastoma
    Neoadjuvant Therapy
    Radiotherapy Dosage
    Radiotherapy, Adjuvant
    Survival Analysis
    Treatment Outcome
    Vincristine

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12697884