Cumulative Cisplatin Dose is Not Associated with Event-free or Overall Survival in Children with Newly Diagnosed Average-risk Medulloblastoma Treated with Cisplatin Based Adjuvant Chemotherapy: Report from the Children's Oncology Group

Background: Survival rates for children with medulloblastoma have risen over the past decade, in part due to the addition of cisplatin-containing adjuvant chemotherapy. Total dose of cisplatin required for optimal treatment is unknown. The purpose of this study was to evaluate the survival outcomes based on cumulative cisplatin doses (CCD) in children with newly diagnosed average-risk medulloblastoma.

Procedure: CCD data were reviewed for 363 patients in a prospective study evaluating patients between 3 and 21 years with a newly diagnosed average-risk medulloblastoma and treated with craniospinal radiation and post-radiation cisplatin based adjuvant chemotherapy.

Results: Eight-year event-free survival (EFS) and overall survival (OS) estimates were 78.2 ± 2.6% and 83.9 ± 2.4%, respectively. Only 73 patients received the protocol specified CCD of 600 mg/m(2), primarily due to mandated cisplatin toxicity-related dose reductions. The median CCD given to those without relapse or death on treatment was 487.5 mg/m(2). CCD, as a time-dependent covariate, was not associated with EFS (P = 0.54) or OS (P = 0.11). The 343 patients who completed chemotherapy failure-free were categorized into four groups according to CCD (n = 10; 75-150 mg/m(2)), (n = 26; 151-300 mg/m(2)), (n = 113; 301-450 mg/m(2)), and (n = 194; 451-600 mg/m(2)). There were no statistically significant differences in distributions of EFS (P = 0.53) or OS (P = 0.49) among these four groups.

Conclusion: CCD is not associated with EFS or OS suggesting that lower doses of cisplatin may be incorporated into future medulloblastoma trials, thereby limiting its toxicity profile without affecting survival. If ototoxicity is encountered, more stringent cisplatin dose modification/cessation rules seem warranted.