PURPOSE: Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. METHODS: We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to the FDA from November 1, 1997 to September 3, 2008. We defined major HAEs, namely agranulocytosis, aplasia, aplastic anemia (AA), leukemia (various), myelodysplastic syndrome (MDS), and lymphoma, and several minor HAEs. RESULTS: A total of 5,127 reports on 3,490 patients were submitted to MedWatch. Among these, we identified 112 cases of major HAEs. Of the 44 reported deaths, the major HAE was considered the cause in 32 cases. The median duration of TMZ treatment was 6 weeks [0.5-108 weeks]. Seventy-six cases of AA or aplasia and 17 cases of leukemia represented the most common major HAE. Important minor HAEs were bone marrow failure and pancytopenia/pancytopenia-like with 325 combined cases; these reports are clinically similar to aplastic anemia. CONCLUSION: The hematologic toxicity profile of TMZ differs from that of other alkylating agents. TMZ HAEs are emerging as significant concerns. Among alkylating agents, AA appears unique to TMZ, and the high rate warrants disclosure of patients. The duration of TMZ exposure prior to the development of AA may be quite short. The risk of AML/MDS is low, but the length of follow-up is insufficient to assess the true risk.
PURPOSE:Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. METHODS: We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to the FDA from November 1, 1997 to September 3, 2008. We defined major HAEs, namely agranulocytosis, aplasia, aplastic anemia (AA), leukemia (various), myelodysplastic syndrome (MDS), and lymphoma, and several minor HAEs. RESULTS: A total of 5,127 reports on 3,490 patients were submitted to MedWatch. Among these, we identified 112 cases of major HAEs. Of the 44 reported deaths, the major HAE was considered the cause in 32 cases. The median duration of TMZ treatment was 6 weeks [0.5-108 weeks]. Seventy-six cases of AA or aplasia and 17 cases of leukemia represented the most common major HAE. Important minor HAEs were bone marrow failure and pancytopenia/pancytopenia-like with 325 combined cases; these reports are clinically similar to aplastic anemia. CONCLUSION: The hematologic toxicity profile of TMZ differs from that of other alkylating agents. TMZ HAEs are emerging as significant concerns. Among alkylating agents, AA appears unique to TMZ, and the high rate warrants disclosure of patients. The duration of TMZ exposure prior to the development of AA may be quite short. The risk of AML/MDS is low, but the length of follow-up is insufficient to assess the true risk.
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