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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

Lookup NU author(s): Professor David Ellison, Dr Helen Lucraft, Dr Richard Gilbertson

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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/m(2) weekly for 10 weeks and four cycles of etoposide 100 mg/m(2) daily for 3 days, and carboplatin 500 mg/m(2) daily for 2 days alternating with cyclophosphamide 1.5 g/m(2). Patients and Methods: Patients aged 3 to 16 years inclusive were randomly assigned to receive 35 Gy craniospinal RT with a 20 Gy posterior fossil 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. J Clin Oncol 21:1581-1591. (C) 2003 by American Society of Clinical Oncology.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Oncology

Year: 2003

Volume: 21

Issue: 8

Pages: 1581-1591

ISSN (print): 0732-183X

ISSN (electronic): 1527-7755

Publisher: American Society of Clinical Oncology

URL: http://dx.doi.org/10.1200/JCO.2003.05.116

DOI: 10.1200/JCO.2003.05.116

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