Sorafenib

Sorafenib

Clinical data
Synonyms	Nexavar Sorafenib tosylate
[[Regulation of therapeutic goods |Template:Engvar data]]	EU EMA: by INN US FDA: Sorafenib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE05 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	29-49%
Protein binding	99.5%
Metabolism	Hepatic oxidation and glucuronidation (CYP3A4-mediated)
Elimination half-life	25–48 hours
Excretion	Fecal (77%) and renal (19%)
Identifiers
IUPAC name 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino] phenoxy]-N-methyl-pyridine-2-carboxamide
CAS Number	284461-73-0
PubChem CID	216239
DrugBank	APRD01304
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C21H16ClF3N4O3
Molar mass	464.825 g/mol
3D model (JSmol)	Interactive image
SMILES CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F

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Evidence Based Medicine
Cochrane Collaboration on Sorafenib Bandolier on Sorafenib TRIP on Sorafenib
Clinical Trials
Ongoing Trials on Sorafenib at Clinical Trials.gov Trial results on Sorafenib Clinical Trials on Sorafenib at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Sorafenib NICE Guidance on Sorafenib NHS PRODIGY Guidance FDA on Sorafenib CDC on Sorafenib
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Definitions
Definitions of Sorafenib
Patient Resources / Community
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Healthcare Provider Resources
Symptoms of Sorafenib Causes & Risk Factors for Sorafenib Diagnostic studies for Sorafenib Treatment of Sorafenib
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International
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Experimental / Informatics
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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 for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials.

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.

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.

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. .

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.

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
• Clinical trial number NCT00217399 at ClinicalTrials.gov - 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.