Regorafenib

Structural formula
General
Non-proprietary name	Regorafenib
other names	4- [4 - ({[4-chloro-3- (trifluoromethyl) phenyl] carbamoyl} amino) -3-fluorophenoxy] - N -methylpyridine-2-carboxamide hydrate
Molecular formula	C 21 H 15 ClF 4 N 4 O 3
Brief description	white to slightly pale reddish yellow solid
External identifiers / databases
CAS number 755037-03-7 EC number 815-051-1 ECHA InfoCard 100.248.939 PubChem 11167602 ChemSpider 9342697 DrugBank DB08896 Wikidata Q3891664
Drug information
ATC code	L01 XE21
Drug class	Cytostatic
Mechanism of action	Tyrosine kinase inhibitor
properties
Molar mass	482.82 g mol −1
Physical state	firmly
Melting point	208 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 302-361fd-373 P: 201-260-264-270-280-308 + 313
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Regorafenib is a tyrosine kinase inhibitor that is currently being investigated for use in various tumor types. For the treatment of colorectal cancer , it has been approved in the USA since 2012 and in the EU since 2013. Regorafenib is also approved for the second-line treatment of hepatocellular carcinoma . Currently (2/2015) a phase II study for the treatment of choroidal neovascularizations of the retina (wet macular degeneration ) is being carried out in Germany. The aim is to obtain approval for use as eye drops.

application areas

Regorafenib is currently used to treat metastatic colorectal cancer in adults when the first few treatments have not had the desired effect. It is also used for the treatment of gastrointestinal stromal tumor (GIST). In August 2017, Bayer also received European approval for the second-line treatment of liver cell carcinoma.

effect

Regorafenib acts through the inhibition of various kinases (VEGFR, TIE2, KIT, RET, RAF-1, BRAF, BRAFV600E, PDGFR, FGFR) antitumoral and anti-angiogenesis . The new benefit assessment of the drug recently showed an average survival benefit of 1.5 months.

Side effects

Common undesirable side effects are weakness , exhaustion , loss of appetite , decreased food intake, hand and foot syndrome , diarrhea , weight loss, infections , high blood pressure, and voice disorders.

In addition Regorafenib is toxic to the liver . By breaking down via CYP3A4 and UGT1A9, it also has the potential for various drug interactions .

Withdrawal from the market

On March 17, 2016, the Federal Joint Committee decided not to award regorafenib (Stivarga®) any additional benefit in the treatment of adults with metastatic colorectal cancer (CRC) compared to the best possible supportive treatment. The pharmaceutical manufacturer Bayer then withdrew the drug from the German market because it saw no way of achieving an economically acceptable price in negotiations with the health insurance companies.

swell

1. ↑ ^{a b c d} Entry on regorafenib at TCI Europe, accessed on October 11, 2018.
2. ↑ FY 2012 Innovative Drug Approvals , FDA Report, page 14, accessed August 8, 2017
3. ↑ EMA - Regorafenib - Authorization details .
4. ↑ ^{a b} Bayer receives EU approval for Stivarga® for the second-line treatment of liver cell carcinoma , report on oncotrends.de, accessed on August 8, 2017
5. ↑ Research - The Bayer research magazine .
6. ↑ Summary of the EPAR for the public , EPAR of the EMA, accessed on August 8, 2017
7. ↑ Regorafenib - benefit assessment .
8. ↑ EMA: Stivarga Regorafenib .