Sunitinib
From Wikipedia, the free encyclopedia
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Sunitinib
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| Systematic (IUPAC) name | |
| N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2- dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4- dimethyl-1H-pyrrole-3-carboxamide |
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| Identifiers | |
| CAS number | ? |
| ATC code | L01 |
| PubChem | |
| Chemical data | |
| Formula | C22H27FN4O2 |
| Mol. mass | 398.474 g/mol 532.561 g/mol (malate) |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 95% |
| Metabolism | Hepatic (CYP3A4-mediated) |
| Half life | 40 to 60 hours (sunitinib) 80 to 110 hours (metabolite) |
| Excretion | Fecal (61%) and renal (16%) |
| Therapeutic considerations | |
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| Routes | Oral |
Sunitinib (marketed as Sutent, previously known as SU11248) is a small molecule receptor tyrosine kinase inhibitor that is approved for the treatment of gastrointestinal stromal tumor (GIST) and renal cell carcinoma (RCC).
Sunitinib inhibits signaling through multiple receptor tyrosine kinases, including platelet-derived growth factor receptor and vascular endothelial growth factor receptor. GIST is driven by a mutationally activated kit kinase, and this is also inhibited by Sunitinib.
Sunitinib is primarily being used in patients with GIST who have disease progression during prior treatment with imatinib (another kit inhibitor) or those who did not tolerate imatinib. In one clinical trial of this patient population, the time to progression was significantly longer in the sunitinib arm than the placebo arm (27 v 6 weeks). Data on overall survival are not mature yet.
Notable side effects included diarrhea, hypertension, skin discoloration, mucositis, fatigue, and hypothyroidism. Neutropenia, thrombocytopenia, and decreases in left ventricular ejection fraction have also been seen with sunitinib.
Efficacy in renal cell carcinoma is probably through inhibition of vascular endothelial growth factor receptor. RCC is one of the most highly vascularized of tumors and is also being targeted by other angiogenesis inhibitors. These inhibitors in theory should have efficacy against many solid tumors, and sunitinib is currently in trials for breast, colon and lung cancers.
Sunitinib was developed by SUGEN, a South San Francisco biotechnology company focused on kinase inhibitors in oncology. SUGEN was acquired by Pharmacia and Upjohn in 1999, and later merged into Pfizer in 2003. Pfizer continued Phase III trials and registration and marketing of the drug. Sunitinib was approved by the FDA for RCC and GIST on January 26, 2006. A clinical trial reported in January 2007 on the New England Journal of Medicine showed significant benefit of sunitinib over interferon alpha (median progression free survival 11 months for patients on sunitinib versus 5 months for those on interferon alpha).[1] It also reported significantly fewer side effects with sunitinib as compared to interferon alpha.
[edit] References
- ^ Motzer RJ et al. (2007). "Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma". N Engl J Med 356 (2): 115–124. PMID 17215529.
[edit] External links
- GIST Support International, An international organization for the support of GIST patients, families, and friends. Includes detailed information from some of the foremost experts on GIST, links to research, treatment options, GIST registry.
