Rational approaches to the chemotherapy of medulloblastoma

Medulloblastoma is the most common primary tumor of the CNS in childhood. Surgical intervention alone will not cure this tumor, and the addition of whole neuraxis irradiation has led to a 50 to 60 per cent, 5-year survival. The role of adjuvant chemotherapy is unclear, although certain subgroups of high-risk patients may benefit from this modality. Agents that have demonstrated activity against recurrent disease include vincristine, cyclophosphamide, cisplatin, methotrexate, dibromodulcitol, and the combination of procarbazine-vincristine-CCNU. However, responses are generally transient and virtually no cures are reported. New, rationally selected agents are clearly needed. In vitro and in vivo models of human medulloblastoma using the medulloblastoma-derived cell lines TE-671 and D283 Med may allow such an approach. Phase II trials using the drugs effective in these models may identify active agents that will ultimately increase survival when used in an adjuvant setting.