TY - JOUR
T1 - Phase II study of sunitinib in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis
AU - Apostolidou, Effrosyni
AU - Kantarjian, Hagop
AU - Thomas, Deborah
AU - Burger, Ian
AU - Borthakur, Gautam
AU - Verstovsek, Srdan
N1 - Funding Information:
This study was funded by grant N01-CM-62202 from the Cancer Therapy Evaluation Program-National Cancer Institute.
PY - 2010/8
Y1 - 2010/8
N2 - 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. Patients and 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. Conclusion: 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.
AB - 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. Patients and 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. Conclusion: 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.
KW - Hydroxyurea
KW - Lenalidomide
KW - Myeloproliferative neoplasm
KW - SU5416
KW - Vatalanib
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U2 - 10.3816/CLML.2010.n.058
DO - 10.3816/CLML.2010.n.058
M3 - Article
C2 - 20709665
AN - SCOPUS:77957068128
SN - 2152-2650
VL - 10
SP - 281
EP - 284
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -