Sorafenib
| Sorafenib
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| Systematic (IUPAC) name | |
| 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino] phenoxy]-N-methyl-pyridine-2-carboxamide | |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C21H16ClF3N4O3 |
| Mol. mass | 464.825 g/mol |
| SMILES | & |
| Synonyms | Nexavar Sorafenib tosylate |
| Pharmacokinetic data | |
| Bioavailability | 29-49% |
| Protein binding | 99.5% |
| Metabolism | Hepatic oxidation and glucuronidation (CYP3A4-mediated) |
| Half life | 25–48 hours |
| Excretion | Fecal (77%) and renal (19%) |
| Therapeutic considerations | |
| Licence data |
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| Routes | Oral |
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Ongoing Trials on Sorafenib at Clinical Trials.gov Clinical Trials on Sorafenib at Google
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Overview
Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). It has also received "Fast Track" designation by the FDA[1] for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials[2].
Pharmacology
It is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.[3]
Approval
Sorafenib was approved by the U.S. Food and Drug Administration (FDA) on December 20, 2005 and received a E.U. marketing authorisation on July 19, 2006[4].
The European Commission has granted marketing authorization to Nexavar® (sorafenib) tablets for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, on October 30, 2007. [5].
Studies
A New England Journal of Medicine article published in January 2007 showed compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02), although this benefit was not statistically significant according to the O'Brien–Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001).
At ASCO 2007, results from the SHARP trial were presented, which showed efficacy of sorafenib in hepatocellular carcinoma. The primary endpoint was overall survival, which showed a 44% improvement in patients who received sorafenib compared to placebo (hazard ratio 0.69; 95% CI, 0.55 to 0.87; p=0.0001). Both median survival and time to progression showed 3-month improvements.
Regulatory filing is planned.
Side effects
Side effects of sorafenib included skin rash, hand-foot skin reactions, diarrhea, and hypertension.
Footnotes
- ↑ https://lnn605.aus.us.siteprotect.com/medicalnews.php?newsid=45119
- ↑ http://www.healthtech.com/news/top_news/2007/June/Nexavar_Extends_Survival.asp
- ↑ SorafenibSunitinibdifferences. Retrieved on 2007-08-15.
- ↑ European Commission - Enterprise and industry. Nexavar. Retrieved April 24,2007.
- ↑ DGnews [1]. Retrieved November 02, 2007.
External links
- Nexavar.com – Manufacturer's website
- Prescribing Information – includes data from the key studies justifying the use of sorafenib for the treatment of kidney cancer (particularly clear cell renal cell carcinoma, which is associated with the von Hippel-Lindau gene)
- Patient Information from FDA
- Sorafenib in Treating Patients With Soft Tissue Sarcomas
- ClinicalTrials.gov NCT00217399 - Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
- [http:/mpablog.typepad.com/david_foster] Two year experience blog on nexavar, sutent, side effects, etc.
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