Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy

Abstract

✓ It has previously been reported in a single-institution trial that progression-free survival of children with medulloblastoma treated with radiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cisplatin, and vincristine chemotherapy during and after radiotherapy was better than the outcome in children treated with radiotherapy alone. To better characterize long-term outcome and duration of disease control, this treatment approach was used for 10 years and expanded to three institutions. Sixty-three children with posterior fossa medulloblastomas were treated with craniospinal local-boost radiotherapy and adjuvant chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligible for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic disease, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factors who received reduced-dose craniospinal radiotherapy (2400 cGy) were also eligible for entry into the study. Sixty-three of 66 eligible patients (95%) were entered and placed on this treatment regimen. Forty-two patients had brainstem involvement, 15 had metastatic disease at the time of diagnosis, and 19 had received a subtotal resection. Progression-free survival for the entire group at 5 years is 85% ± 6%. Three children have succumbed to a second malignancy, and overall 5-year event-free survival is 83% ± 6%. Progression-free survival was not adversely affected by younger age at diagnosis, brainstem involvement, or subtotal resection. Five-year actuarial progression-free survival for patients who received reduced-dose radiotherapy was similar to that for patients receiving conventional-dose radiotherapy. Patients with metastatic disease at the time of diagnosis had a 5-year progression-free survival rate of 67% ± 15%, as compared to 90% ± 6% for those patients with localized disease at the time of diagnosis (p = 0.037). The authors conclude that overall progression-free survival remains excellent for children with posterior fossa medulloblastomas treated with this drug regimen. Chemotherapy has a definite role in the management of children with medulloblastoma. Further studies are indicated to define which subpopulations of children with medulloblastoma benefit from chemotherapy and what regimens are optimum in increasing disease control and, possibly, in reducing the amount of radiotherapy required.