Phase I study of sorafenib in patients with refractory or relapsed acute leukemias

Haematologica. 2011 Jan;96(1):62-8. doi: 10.3324/haematol.2010.030452. Epub 2010 Oct 15.


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 sorafenib-based combinations. ( Identifier: NCT00217646).

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzenesulfonates / therapeutic use*
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / pathology
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / therapeutic use*
  • Remission Induction
  • Salvage Therapy
  • Sorafenib
  • Survival Rate
  • Young Adult


  • Benzenesulfonates
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Sorafenib

Associated data