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Recenzirano
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Carrato Mena, Alfredo; Grande Pulido, Enrique; Guillén-Ponce, Carmen
Anti-cancer drugs, 2010-January, 2010-Jan, 2010-01-00, 20100101, Letnik: 21 Suppl 1, Številka: Supplement 1Journal Article
Sunitinib is an orally available small-molecule multikinase inhibitor. This agent potently inhibits the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit in addition to other kinases in biochemical and cell-based assays. In several relevant preclinical cancer models, sunitinib exerts significant antiangiogenesis and antitumor effects. In phase I studies, using intermittent dosing schedules, oral administration of doses up to 50 mg/day were reasonably well tolerated and resulted in plasma concentrations in the range of targeted levels needed for sustained kinase inhibition. Biomarker and functional imaging studies showed modulation of circulating markers of angiogenesis as well as a reduction in tumor metabolism. Sunitinib showed clinical activity in patients with renal cell cancer and in patients with imatinib-resistant gastrointestinal stromal tumors. Definitive randomized clinical trials showed significant clinical activity in these two indications leading to regulatory approval. In addition, this drug has showed activity in a variety of other tumor types such as breast, colon, and lung cancer and is being explored in combination with standard drugs in these diseases. The observation that biological and functional imaging effects are reduced during drug-free intervals has prompted the evaluation of protracted dosing schedules. A better understanding of mechanisms involved in resistance to sunitinib provides the rationale for combination strategies that hopefully will result in better clinical effect. Ongoing studies will elucidate the overall role of this drug in cancer treatment.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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