Feasibility of an Attenuated Maintenance Chemotherapy Regimen Directed at Adolescents and Young Adults with Newly Diagnosed Localized Medulloblastoma and Other Central Nervous System Embryonal Tumors

Abstract

Purpose: Newly diagnosed adolescents and young adults (AYAs) with medulloblastoma experience substantial toxicities with “standard” maintenance chemotherapy regimens that include lomustine, cisplatin, and vincristine. An attenuated maintenance chemotherapy regimen targeting AYAs was evaluated for toxicity and tolerability. Methods: Eleven patients with central nervous system (CNS) malignant embryonal tumors treated between 2004 and 2010 at five institutions were evaluated. Three patients were <17 years old, seven were aged 17–39, and one was 50 years old. Seven were female. Detailed toxicity data were evaluated. Results: Eighty-seven cycles were administered (87% of all planned cycles). Grade 3/4 neutropenia occurred in 60% of cycles, with the use of granulocyte growth factor support in only 15% of cycles. Grade 3/4 anemia and thrombocytopenia occurred in 33% and 29% of cycles, respectively; however, blood and platelet transfusions were administered in only 32% and 21% of cycles, respectively. Grade 3/4 transaminitis occurred in 8% of cycles. There were five grade 2 reports of anorexia, one grade 3 sensory and four grade 3 motor neuropathies, and one grade 3 hypocalcemia and hypomagnesemia. No grade 1–4 ototoxicities or nephrotoxicities were observed. No grades 3 or 4 weight loss was observed. Two patients had single hospitalizations for chemotherapy-related toxicities (1 and 13 days in duration). After 3.5 years median follow-up, only the single patient with atypical teratoid/rhabdoid tumor had relapsed. Conclusion: This attenuated maintenance chemotherapy regimen was well tolerated by AYAs. A prospective North American clinical trial is planned for AYAs with CNS embryonal tumors to determine the efficacy of this regimen.