TREATMENT OF HIGH-RISK MEDULLOBLASTOMA AND OTHER PRIMITIVE NEUROECTODERMAL TUMORS WITH REDUCED DOSE CRANIOSPINAL RADIATION-THERAPY AND MULTIAGENT NITROSOUREA-BASED CHEMOTHERAPY

Purpose: To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblas toma, and other primitive neuroectodermal tumors (PNET) with a combine d modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy. Patients and Methods: Between 1984 and 1992, 34 evaluab le patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniosp inal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulci tol were given before lomustine (CCNU) to enhance CCNU-induced tumor c ell kill and to reduce alkyltransferase repair of ethylated DNA. Vincr istine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was gi ven in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the n euroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer. Results: Patients treated included 27 with medullobl astoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bu lky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years . The 5-year survival estimate is 56%. One patient had inadequate stag ing to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M 1 or higher stage) who had a 3-and 5-year PFS of 42 and 21% respectively and 5-year surv ival of 42%. There were 14 patients who had negative staging (MO stage ) who had a 3-and 5-year PFS of 69 and 52% respectively and 5-year sur vival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or hi gher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with MO stagin g had a 5-year PFS and overall survival of 52 and 73% respectively. Ov erall toxicity was primarily due to mild hematological toxicity and re lated to the use of the chemotherapy. Conclusions: The results using t his therapy in high-risk groups of patients does not offer any improve ment over results reported in other recent studies. The reason for the se results may be due to the lowered craniospinal radiation dose.