Sorafenib

verifiedrevid	464405524
width	300
image2	Sorafenib 3D 3gcs.png
width2	250
tradename	Nexavar, others
medlineplus	a607051
dailymedid	Sorafenib
licence eu	yes
licence us	Sorafenib
pregnancy au	D
routes of administration	By mouth
atc prefix	L01
atc suffix	EX02
legal au	S4
legal ca	Rx-only
legal uk	POM
legal us	Rx-only
legal eu	Rx-only
legal eu comment	‡R1R‡
bioavailability	38–49%
protein bound	99.5%
metabolism	Liver oxidation and glucuronidation (CYP3A4 & UGT1A9-mediated)
elimination half-life	25–48 hours
excretion	Feces (77%) and urine (19%)
cas number	284461-73-0
pubchem	216239
iuphar ligand	5711
drugbank	DB00398
chemspiderid	187440
unii	9ZOQ3TZI87
kegg	D08524
kegg2	D06272
chebi	50924
chembl	1336
pdb ligand	BAX
synonyms	Sorafenib tosylate
iupac name	4-[4- [[ 4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino] phenoxy]-N-methyl-pyridine-2-carboxamide\| C=21 \| H=16 \| Cl=1 \| F=3 \| N=4 \| O=3\| SMILES = CNC(=O)c1cc(ccn1)Oc2ccc(cc2)NC(=O)Nc3ccc(c(c3)C(F)(F)F)Cl\| StdInChI = 1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)\| StdInChI_comment = \| StdInChIKey = MLDQJTXFUGDVEO-UHFFFAOYSA-N\| density = \| density_notes = \| melting_point = \| melting_high = \| melting_notes = \| boiling_point = \| boiling_notes = \| solubility = \| sol_units = \| specific_rotation = \|undefined

Sorafenib, sold under the brand name Nexavar,[2] is a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (hepatocellular carcinoma), FLT3-ITD positive AML and radioactive iodine resistant advanced thyroid carcinoma.

Mechanism of action

Sorafenib is a protein kinase inhibitor with activity against many protein kinases, including VEGFR, PDGFR and RAF kinases.[3] Of the RAF kinases, sorafenib is more selective for c-Raf than B-RAF.[4] (See BRAF (gene) for details the drug's interaction with B-Raf.)

Sorafenib treatment induces autophagy,[5]

Medical uses

Sorafenib is indicated as a treatment for advanced renal cell carcinoma (RCC), unresectable hepatocellular carcinomas (HCC), thyroid cancer and Acute Myeloid Leukaemia with FLT3-ITD mutation..[7][8][9][10]

Kidney cancer

Clinical trial results, published January 2007, showed that, 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).[11]

In Australia this is one of two TGA-labelled indications for sorafenib, although it is not listed on the Pharmaceutical Benefits Scheme for this indication.[10]

Liver cancer

At ASCO 2007, results from the SHARP trial[12] were presented, which showed efficacy of sorafenib in hepatocellular carcinoma. The primary endpoint was median 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; however, there was no significant difference in median time to symptomatic progression (p=0.77). There was no difference in quality of life measures, possibly attributable to toxicity of sorafenib or symptoms related to underlying progression of liver disease. Of note, this trial only included patients with Child-Pugh Class A (i.e. mildest) cirrhosis.[12] Because of this trial sorafenib obtained FDA approval for the treatment of advanced hepatocellular carcinoma in November 2007.

In a randomized, double-blind, phase II trial combining sorafenib with doxorubicin, the median time to progression was not significantly delayed compared with doxorubicin alone in patients with advanced hepatocellular carcinoma. Median durations of overall survival and progression-free survival were significantly longer in patients receiving sorafenib plus doxorubicin than in those receiving doxorubicin alone.[13]

Thyroid cancer

On 22 November 2013, sorafenib was approved by the FDA for the treatment of locally recurrent or metastatic, progressive differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment.[16]

The phase III DECISION trial showed significant improvement in progression-free survival but not in overall survival. However, as is known, the side effects were very frequent, specially hand and foot skin reaction.[17]

Acute Myeloid Leukaemia

In patients with FLT3-ITD mutated AML, sorafenib can be used as a maintenance therapy post-Allogeneic haematopoietic stem-cell transplantation to target any residual disease that could remain in the bone marrow.[18]

References

Nexavar EPAR European Medicines Agency (EMA), 17 September 2018, retrieved 18 September 2022^

FDA Approves Nexavar for Patients with Inoperable Liver Cancer FDA, 19 November 2007, retrieved 10 November 2012^

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling Molecular Cancer Therapeutics, October 2008^

CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations Oncogene, January 2009^

Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways Molecular Medicine Reports, January 2014^

Encyclopedia of Molecular Pharmacology Springer, Cham, 30 March 2020^

Nexavar (sorafenib) dosing, indications, interactions, adverse effects, and more Medscape Reference, WebMD, retrieved 26 December 2013^

Nexavar (sorafenib) tablet, film coated [Bayer HealthCare Pharmaceuticals Inc.] DailyMed, Bayer HealthCare Pharmaceuticals Inc., November 2013, retrieved 26 December 2013^

Nexavar 200mg film-coated tablets - Summary of Product Characteristics (SPC) - (eMC) electronic Medicines Compendium, Bayer plc, 27 March 2013, retrieved 26 December 2013^

PRODUCT INFORMATION NEXAVAR (sorafenib tosylate) TGA eBusiness Services, Bayer Australia Ltd, 12 December 2012, retrieved 26 December 2013^

Sorafenib in advanced clear-cell renal-cell carcinoma The New England Journal of Medicine, January 2007^

Sorafenib in advanced hepatocellular carcinoma The New England Journal of Medicine, July 2008^

Sorafenib: a review of its use in advanced hepatocellular carcinoma Drugs, 2009^

Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma Journal of Clinical Oncology, October 2011^

Pharmaceutical Benefits Scheme (PBS) -SORAFENIB Pharmaceutical Benefits Scheme, Australian Government Department of Health, retrieved 27 December 2013^

FDA Approval for Sorafenib Tosylate National Cancer Institute, 5 October 2006, retrieved 27 November 2013^

ASCO: Sorafenib Halts Resistant Thyroid Cancer www.medpagetoday.com, 4 June 2013, retrieved 21 December 2018^

Data Show Sorafenib Maintenance Therapy After Allo-HSCT Improves Outcomes in FLT3-ITD-Positive AML Hematology Advisor, 29 July 2020, retrieved 27 December 2025^

Low blood phosphate levels^

Bleeding; including serious bleeds such as intracranial and intrapulmonary bleeds^

High blood pressure^

Including abdominal pain, headache, tumour pain, etc.^

Considered a low (~10-30%) risk chemotherapeutic agent for causing emesis)^

Chemotherapy-Induced Nausea and Vomiting Treatment & Management Medscape Reference, WebMD, 3 July 2012, retrieved 26 December 2013^

Low level of white blood cells in the blood^

Low level of neutrophils in the blood^

Low level of red blood cells in the blood^

Low level of plasma cells in the blood^

Low blood calcium^

Low blood potassium^

Hearing ringing in the ears^

Heart attack^

Lack of blood supply for the heart muscle^

Mouth swelling, also dry mouth and glossodynia^

Indigestion^

Not being able to swallow^

Sore joints^

Muscle aches^

Kidney failure^

Excreting protein [usually plasma proteins] in the urine. Not dangerous in itself but it is indicative kidney damage^

Including skin reactions and urticaria (hives)^

Underactive thyroid^

Overactive thyroid^

Low blood sodium^

Runny nose^

Pneumonitis, radiation pneumonitis, acute respiratory distress, etc.^

Swelling of the pancreas^

Swelling of the stomach^

Formation of a hole in the gastrointestinal tract, leading to potentially fatal bleeds^

Yellowing of the skin and eyes due to a failure of the liver to adequately cope with the amount of bilirubin produced by the day-to-day actions of the body^

Swelling of the gallbladder^

Swelling of the bile duct^

A potentially fatal skin reaction^

A fairly benign form of skin cancer^

Unusually Severe Bullous Skin Reaction to Sorafenib: A Case Report Journal of Medical Cases, August 2010^

A potentially fatal abnormality in the electrical activity of the heart^

Swelling of the skin and mucous membranes^

A potentially fatal allergic reaction^

Swelling of the liver^

The rapid breakdown of muscle tissue leading to the build-up of myoglobin in the blood and resulting in damage to the kidneys^

FDA Approval letter for use of sorafenib in advanced renal cancer retrieved 19 November 2009^

Nexavar Enterprise and Industry., European Commission, retrieved 24 April 2007^

FDA Approval letter for use of sorafenib in inoperable hepatocellular carcinoma retrieved 19 November 2009^

Liver drug 'too expensive' BBC News, 19 November 2009, retrieved 10 November 2012^

» Supreme Court says no to Bayer, upholds compulsory license on Nexavar^

Application for Compulsory Licence Under Section 84(1) of the Patents Act, 1970 in Respect of Patent No.215758 Controller of Patents Mumbai, retrieved 2 April 2012^

Indian generics Nature, 9–15 March 2012^

India Patents (Amendment) Act, 2005 WIPO, retrieved 16 January 2013^

Bloomberg's viral misquote Columbia Journalism Review, 29 January 2014, retrieved 12 September 2019^

Addition of Sorafenib May Be Detrimental in Some Lung Cancer Patients MedScape, April 25, 2008, retrieved 29 October 2010^

Clinical outcome of treatment with serine-threonine kinase inhibitors in recurrent epithelial ovarian cancer: a systematic review of literature Expert Opinion on Investigational Drugs, July 2016^

{{ClinicalTrialsGov|NCT00329719|Sorafenib and Temsirolimus in Treating Patients With Recurrent Glioblastoma}}^

Activity of Sorafenib against desmoid tumor/deep fibromatosis Clinical Cancer Research, June 2011^

Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis Clinicaltrials.gov, retrieved 12 November 2014^

Activity of Sorafenib against desmoid tumor/deep fibromatosis Clinical Cancer Research, June 2011^

Desmoid Tumors: Current Perspective and Treatment Current Treatment Options in Oncology, February 2024^

Sorafenib

Mechanism of action

Medical uses

Kidney cancer

Liver cancer

Thyroid cancer

Acute Myeloid Leukaemia

Adverse effects

History

Renal cancer

Liver cancer

Society and culture

Nexavar controversy

Research

Lung

Ovarian cancer

Brain (recurrent glioblastoma)

Desmoid tumor (aggressive fibromatosis)

See also

External links

References