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Adjuvant Chemotherapy in the Treatment of Localized Medulloblastoma in Children 791

Medulloblastoma (MB) is the most common malignant brain tumor of the posterior fossa in children. Surgical excision followed by neuraxis radiation has been the mainstay of therapy for children with localized posterior fossa(PF) MB. This treatment has resulted in a 60-65% long term disease free survival. In an effort to improve the outcome of children with this chemosensitive tumor, some institutions have incorporated adjuvant chemotherapy into the initial therapeutic regimen. Between 5/92 and 1/97, 12 children (mean age 10 years 3 months) presented consecutively with localized PF MB. Magnetic resonance imaging of the spine showed no evidence of metastatic disease. All patients underwent gross total surgical excision of the primary tumor followed by total neuraxis irradiation, and then treatment with 6 cycles of multiagent chemotherapy. The median radiation doses to the spinal axis, brain, and tumor were 3600 cGy, 4000 cGy and 5450 cGy, respectively. Following radiation therapy, all patients were treated with cycles of vincristine 2 mg/m2 IV, methylprednisolone 300 mg/m2 IV every six hours for three doses, cisplatin 90 mg/m2 IV, and cyclophosphamide 1200 mg/m2 IV. G-CSF was subsequently administered until neutrophil recovery. Chemotherapy cycles were administered every 3-4 weeks. Nine of twelve (75%) patients received 6 of 6 scheduled cycles of chemotherapy with 68 of 72 planned cycles administered overall. At a mean duration from diagnosis of 3 years, all patients remain disease-free. Hematopoietic toxicity predominated with grade III/IV neutropenia and thrombocytopenia following 66% and 32% respectively, of administered cycles of chemotherapy. Infectious complications included 13 episodes of fever and neutropenia (4 with positive blood cultures), 2 episodes of cellulitis and 2 episodes of herpes zoster. GI and renal toxicities were minimal with one episode each of pancreatitis, ileus and hepatic enzyme elevation; 2 episodes of transient reduction in creatinine clearance (25-49%); and 6 episodes of electrolyte imbalance. One patient developed severe unilateral hearing loss. Transfusion support with packed red blood cells and platelets was required following 40% and 10%, of administered cycles of chemotherapy respectively. Dose modification due to toxicity occurred following 42% of cycles of therapy, and 50% of patients required nutritional support. This regimen was well tolerated with the major toxicity being hematopoietic. While longer follow up is necessary, this regimen shows promise for improved clinical outcome in children with PF MB.