Phase II study of sunitinib in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.
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.
Apostolidou
Effrosyni
E
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Kantarjian
Hagop
H
Thomas
Deborah
D
Burger
Ian
I
Borthakur
Gautam
G
Verstovsek
Srdan
S
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*
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib