Background: Newly-diagnosed adolescents and adults with medulloblastoma experience substantial toxicities with “standard” maintenance chemotherapy regimens including CCNU, cisplatin and vincristine. We evaluated an attenuated maintenance chemotherapy regimen targeting adolescents and adults. Methods: Eleven patients with newly-diagnosed medulloblastoma and 1 suprasellar atypical teratoid/rhabdoid tumor (AT/RT) were treated between 2004 and 2010. Eight patients were between 17 and 50 years old. Nine were female. Eleven received 2340cGy craniospinal irradiation, 1 AT/RT 3600cGy, all with standard posterior fossa or tumor bed boosts. Ten patients received weekly vincristine x 6 (1.5mg/M², max. 2mg) during irradiation. Maintenance chemotherapy was initiated 4-6 weeks following irradiation: Cycle A: vincristine (days 1, 8), oral temozolomide (150mg/m² days 1-5) and oral etoposide (50mg/M² days 1-21), Cycle B: vincristine (days 1, 8), carboplatin day 1 (560mg/M²). Cycle C: vincristine (days 1, 8), cyclophosphamide (600mg/M² on days 1 and 2). Cycles A, B and C were repeated for 9 total cycles. Retrospective collection of toxicity and outcome data was approved by institutional IRBs for all patients. Results: A total of 87 cycles were administered. Grades III/IV neutropenia occurred in 71% cycles, anemia in 37% cycles and thrombocytopenia in 29% cycles. Grades 3/4 transaminitis occurred in 8% cycles. There were 5 grade 2 reports of anorexia, 1 grade 3 sensory and 4 grade 3 motor neuropathies and one grade 3 hypocalcemia. No grades 1-IV ototoxicities or nephrotoxicities were observed. No grades 3/4 weight loss were observed. Two patients had single hospitalizations for chemotherapy-related toxicities (1 and 13 days’ duration). After 3 years median follow-up, no patient with medulloblastoma relapsed; the ATRT patient recurred 24 months from diagnosis. Conclusions: This attenuated maintenance chemotherapy regimen was well tolerated by adolescents and adults. A prospective North American clinical trial is planned for adult medulloblastoma/PNET to determine the efficacy of this regimen.