A Phase I/II Study of Sorafenib in Combination With Low Dose Cytarabine in Elderly Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome From the National Cancer Institute of Canada Clinical Trials Group: Trial IND.186

Leuk Lymphoma. 2013 Apr;54(4):760-6. doi: 10.3109/10428194.2012.737917. Epub 2012 Nov 15.


Sorafenib is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The National Cancer Institute of Canada (NCIC) Clinical Trials Group initiated a phase I/II study of the combination of sorafenib with cytarabine in older patients with AML or high-risk MDS who were unsuitable for intensive chemotherapy. FLT3 mutational status was determined in all patients. Twenty-one patients were enrolled (four MDS, 17 AML) with a median age of 77 years. The recommended phase II dose (RP2D) was cytarabine 10 mg bid days 1-10 and sorafenib 600 mg/day days 2-28. Dose-limiting toxicities were fatigue, sepsis and skin rash. Of 15 evaluable patients treated at the RP2D, two patients responded. The overall response rate for eligible patients was 10%. FLT3 mutations were found in only three patients. We conclude that this combination of sorafenib and cytarabine has limited activity in this unselected cohort of elderly patients with AML/MDS in which FLT3 mutations seemed underrepresented.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cytarabine / administration & dosage
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Male
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Sorafenib
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics


  • Phenylurea Compounds
  • Cytarabine
  • Niacinamide
  • Sorafenib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3