OUTCOME FOR CHILDREN WITH MEDULLOBLASTOMA TREATED WITH RADIATION AND CISPLATIN, CCNU, AND VINCRISTINE CHEMOTHERAPY

It has previously been reported in a single-institution trial that pro gression-free survival of children with medulloblastoma treated with r adiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso (CCNU), cispl atin, and vincristine chemotherapy during and after radiotherapy was b etter 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 medulloblastom as were treated with craniospinal local-boost radiotherapy and adjuvan t chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligib le for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic diseas e, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factors who received reduced-dose craniosp inal radiotherapy (2400 cGy) were also eligible for entry into the stu dy. Sixty-three of 66 eligible patients (95%) were entered and placed on this treatment regimen. Forty-two patients had brainstem involvemen t, 15 had metastatic disease at the time of diagnosis, and 19 had rece ived a subtotal resection. Progression-free survival for the entire gr oup at 5 years is 85% +/- 6%. Three children have succumbed to a secon d malignancy, and overall 5-year event-free survival is 83% +/- 6%. Pr ogression-free survival was not adversely affected by younger age at d iagnosis, brainstem involvement, or subtotal resection. Five-year actu arial 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 dia gnosis had a 5-year progression-free survival rate of 67% +/- 15%, as compared to 90% +/- 6% for those patients with localized disease at th e time of diagnosis (p = 0.037). The authors conclude that overall pro gression-free survival remains excellent for children with posterior f ossa medulloblastomas treated with this drug regimen. Chemotherapy has a definite role in the management of children with medulloblastoma. F urther studies are indicated to define which subpopulations of childre n with medulloblastoma benefit from chemotherapy and what regimens are optimum in increasing disease control and, possibly, in reducing the amount of radiotherapy required.