Sorafenib (Nexavar,) has been approved for the treatment of metastatic renal cancer and advanced hepatocellular carcinoma. It inhibits the serine threonine kinase RAF-1, but also the FLT3-RTK and FLT3-ITD, suggesting that it may have a role in treating AML with FLT3 mutations. Sorafenib is a FLT3 tyrosine kinase inhibitor, and approximately 25 percent of patients with de novo AML have the FLT3 mutation. Sorafenib in a phase 1 clinical trial on 16 patients with AML was found to be active in 6 of the 7 Flt3-ITD–positive patients. Response in FLT negative patients was 15%. However, treatment duration was short (21-70 days), and no durable responses were reported. Notably, a complete molecular remission has recently been reported in a patient relapsing after stem cell transplantation (SCT). More recently, higher responses were reported in FLT3 negative patients.
There is a high degree of interest in the use of sorafenib with other drugs or alone for FLT+ AML and there are a number of recent publications corroborating its effectiveness. Although NCCN (AML-E) does not yet list this treatment, there is significant literature support and few other options in relapsed AML. However, its use front-line or for consolidation or maintenance is not literature supported.
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