Regorafenib

Systematic (IUPAC) name
4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrate
Clinical data
Trade names Stivarga
Licence data US FDA:link
  • AU: D
  • US: D (Evidence of risk)
Oral
Pharmacokinetic data
Bioavailability 69-83%
Protein binding 99.5%
Metabolism Hepatic (UGT1A9-mediated)
Half-life 20-30 hours
Excretion Faeces (71%), urine (19%)
Identifiers
755037-03-7
L01XE21
PubChem CID 11167602
ChemSpider 28295228
KEGG D10138
ChEBI CHEBI:68647 Yes
ChEMBL CHEMBL1946170
Synonyms BAY 73-4506
Chemical data
Formula C21H17ClF4N4O4
482.82 g mol

Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition. It is currently being studied as a potential treatment option in multiple tumor types.[1]

Approvals and indications

Metastatic colorectal cancer

Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer[2] and has been approved by the US FDA on September 27, 2012.[3]

Advanced gastrointestinal stromal tumours

On February 25, 2013 the US FDA expanded the approved use to treat patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease. In a clinical study with 199 patients regorafenib treated patients had a delay in tumor growth (progression-free survival) that was, on average, 3.9 months longer than patients who were given placebo.[4]

Adverse effects

Regorafenib is being approved with a Boxed Warning alerting patients and health care professionals that severe and fatal liver toxicity occurred in patients treated with regorafenib during clinical studies. Serious side effects, which occurred in less than one percent of patients, were liver damage, severe bleeding, blistering and peeling of skin, very high blood pressures requiring emergency treatment, heart attacks and perforations (holes) in the intestines. The most common side effects reported in patients treated with regorafenib include weakness or fatigue, loss of appetite, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhoea, mouth sores (mucousitis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia).[5]

References

  1. ↑ "Bayer Announces New Data on Oncology Portfolio To Be Presented at the ECCO-ESMO Congress 2009". Retrieved 2009-09-19.
  2. ↑ "Phase III Trial of Regorafenib in Metastatic Colorectal Cancer Meets Primary Endpoint of Improving Overall Survival". Retrieved 2011-10-26.
  3. ↑ "FDA approves new treatment for advanced colorectal cancer". 27 Sep 2012.
  4. ↑ "FDA approves Stivarga for advanced gastrointestinal stromal tumors". 25 Feb 2013.
  5. ↑ "FDA Prescribing Information" (PDF). 27 Sep 2012.