کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10908717 | 1087801 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A phase I, open-label, multi-center study of the JAK2 inhibitor AZD1480 in patients with myelofibrosis
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The anti-tumor activity of AZD1480, a potent, selective inhibitor of Janus-associated kinases 1 and 2, was demonstrated in preclinical models of myeloproliferative neoplasms. In a phase I clinical study, 35 patients with myelofibrosis received 2.5-70Â mg AZD1480 orally once daily (QD) or 10 or 15Â mg twice daily (BID) continuously during repeated 28-day cycles. Two patients experienced dose-limiting toxicities: one patient in the 2.5Â mg QD cohort had a grade 3 lung infiltration/acute pneumonia, and one patient receiving 50Â mg QD had grade 3 presyncope. Dosing was stopped at 70Â mg QD after the first patient experienced an adverse neurological event (AE) and evidence of low-grade neurological toxicity in patients on lower doses after the initial month of therapy became apparent. The most common AZD1480-related AEs were dizziness and anemia. AZD1480 was absorbed quickly and eliminated from the plasma rapidly, with a mean terminal half-life of 2.45-8.06Â h; accumulation was not observed after repeated daily dosing for 28 days. Four patients showed evidence of clinical improvement based on IWG-MRT 2006 criteria. AZD1480 was relatively well tolerated, however, low-grade, reversible neurological toxicity was therapy limiting and led to study termination.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 39, Issue 2, February 2015, Pages 157-163
Journal: Leukemia Research - Volume 39, Issue 2, February 2015, Pages 157-163
نویسندگان
Srdan Verstovsek, Ronald Hoffman, John Mascarenhas, Jean-Charles Soria, Ratislav Bahleda, Patricia McCoon, Weifeng Tang, Jorge Cortes, Hagop Kantarjian, Vincent Ribrag,