title: Phase II study of sunitinib in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.
abstract: BACKGROUND
  Changes in the bone marrow microenvironment in myelofibrosis are triggered by a cytokine burst and consist of fibrosis, osteosclerosis, and angiogenesis. Sunitinib is a multitargeted small-molecule inhibitor of the receptor tyrosine kinases involved in cell proliferation and angiogenesis, including vascular endothelial growth factor receptors.
  
  
  METHODS
  Fourteen patients with myelofibrosis were treated with sunitinib at a daily continuous dose of 37.5 mg orally. The median duration of sunitinib treatment was 5.2 months (range, 1-18 months).
  
  
  RESULTS
  One patient (7%) showed a clinical improvement of anemia (increase in hemoglobin of 4 g/dL), with improvement in anemia-associated symptoms. The time to response was 6 months, and the benefit was sustained for 12 months. However, 8 patients (57%) experienced a total of 13 incidents of significant (grade 3-4) adverse events possibly related to sunitinib (fatigue, gastrointestinal disturbances, anemia, leukopenia, and thrombocytopenia were the most common). In 7 patients (50%), sunitinib was held, and subsequently the dose was reduced to 25 mg daily. Overall, 29% of patients withdrew from the study because of toxicity.
  
  
  CONCLUSIONS
  Sunitinib therapy, as applied here, was not well-tolerated by patients with myelofibrosis, and the benefits were minimal. Our experience with sunitinib combined with previous experience with other antiangiogenic medications suggest that this class of drugs may have limited usefulness in myelofibrosis when used as a single-agent therapy.
authors: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Effrosyni
authors: E
authors: Apostolidou
authors: Hagop
authors: H
authors: Kantarjian
authors: Deborah
authors: D
authors: Thomas
authors: Ian
authors: I
authors: Burger
authors: Gautam
authors: G
authors: Borthakur
authors: Srdan
authors: S
authors: Verstovsek
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000188:drug therapy*; D055728:Primary Myelofibrosis / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D013920:Thrombocythemia, Essential / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib