Limiting toxicity in medulloblastoma treatment

Medulloblastoma is the most common malignant brain tumor of childhood. For children diagnosed at age 3 years or later, the five-year survival rate is 60 to 70 percent. Recent increases in survival rates are likely due to improved treatment strategies, which include radiation therapy and cisplatin-based adjuvant chemotherapy.

However, these treatment regimens carry a significant risk of acute and long-term sequelae that can affect the quality of life of pediatric medulloblastoma survivors. Cisplatin is dose dependent and often associated with irreversible hearing loss, a particularly serious complication for young children whose language is not fully developed. The optimal dose of cisplatin for treatment of medulloblastoma is unknown.

A retrospective study by Amulya A. Nageswara Rao, MBBS, a pediatric hematologist/oncologist at Mayo Clinic in Rochester, Minnesota, and colleagues suggests that cisplatin dosage may be lowered without affecting patients' survival. The study was published in the January 2014 issue of Pediatric Blood & Cancer.

The researchers reviewed cumulative cisplatin dose data from patients enrolled in the Children's Cancer Group/Pediatric Oncology Group (CCG-A9961/POG-A9961) trial, a phase III prospective study evaluating the effectiveness of treatment in patients with a newly diagnosed average-risk medulloblastoma. The study included 363 patients ages 3 to 21 years. All patients were treated with craniospinal radiation and post-radiation cisplatin-based adjuvant chemotherapy.

Analyses of the 343 patients who did not experience a failure on chemotherapy were conducted by categorizing these patients into four groups, based on cumulative cisplatin doses. Among all patients studied:

  • Eight-year, event-free survival (EFS) was 78.2 months
  • Overall survival (OS) was 83.9 months
  • There were no statistically significant differences in distributions of EFS or OS among the four dose groups

The results indicate that cumulative cisplatin dose 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.

For more information

Nageswara Rao AA, et al. 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. Pediatric Blood & Cancer. 2014;61:102.