Hematologic adverse events associated with temozolomide (TMZ)

2053 Background: Secondary acute myeloid leukemia (AML) is reported to occur in 3%-10% of patients treated with alkylating agents for Hodgkin's lymphoma, non-Hodgkin's lymphoma, ovarian cancer, breast cancer, and multiple myeloma. The incidence of secondary AML is greatest at 5–10 years after treatment, and AML often follows myelodysplastic syndrome (MDS). TMZ is a pro-drug of methyl-triazeno-imidazole-carboxamide (MTIC), an alkylating metabolite of dacarbazine. Chemotherapy induced aplastic anemia is usually dose-related versus an idiosyncratic mechanism. A small number of fatal cases of TMZ-induced aplastic anemia have been reported. The FDA, in a Drug Safety Newsletter, described 18 cases of aplastic anemia reported between 1999 and 2006. TMZ use in brain tumors and in melanoma is increasing, with little known on the incidence of severe hematologic adverse events. Methods: We searched the FDA MedWatch database for TMZ and obtained all entries submitted to the FDA from November 1, 1997 to September 3, 2...