Background Sorafenib is a multi-kinase inhibitor with activity against fms-like tyrosine kinase 3 with internal tandem duplication mutation and Raf kinase among others. A phase I dose escalation study of sorafenib was conducted in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. Design and Methods Fifty patients received one of two different schedules; Schedule "A": once or twice daily, five days per week, every week for a 21 day cycle, and Schedule "B": once or twice daily, for 14 days every 21 days. Dose limiting toxicities were grade 3/4 hypertension, hyperbilirubinemia, and amylase elevation. The recommended phase II dose in hematologic malignancies is 400 mg twice daily for both schedules. Results Complete remissions or complete remissions with incomplete recovery of platelets were achieved in 5 (10%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Significant reduction in bone marrow and/or peripheral blood blasts was seen in an additional 17 (34%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Eleven of these responses (including 3 complete remissions/complete remissions with incomplete recovery) lasted for 2 cycles or beyond. In conclusion, sorafenib is active and well tolerated in acute myelogenous leukemia with fms-like tyrosine kinase 3 internal tandem duplication mutation. Conclusions Additional studies of sorafenib in patients with acute myelogenous leukemia, particularly those with fms-like tyrosine kinase 3 internal tandem duplication, are warranted, including sorafenibbased combinations.
- FLT3 mutation
ASJC Scopus subject areas