regorafenib

Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer{{Cite web|url=http://www.press.bayer.com/baynews/baynews.nsf/id/Phase-III-Trial-Regorafenib-Metastatic-Colorectal-Cancer-Meets-Primary-Endpoint-Improving-Overall?Open&ccm=001|title=Phase III Trial of Regorafenib in Metastatic Colorectal Cancer Meets Primary Endpoint of Improving Overall Survival|access-date=October 26, 2011|url-status=dead|archive-url=https://web.archive.org/web/20120119104218/http://www.press.bayer.com/baynews/baynews.nsf/id/Phase-III-Trial-Regorafenib-Metastatic-Colorectal-Cancer-Meets-Primary-Endpoint-Improving-Overall?Open&ccm=001|archive-date=January 19, 2012}} and has been approved by the US FDA in September 2012.{{cite news |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm321271.htm |title=FDA approves new treatment for advanced colorectal cancer |date=September 27, 2012 |access-date=August 30, 2024 |archive-date=January 18, 2017 |archive-url=https://web.archive.org/web/20170118091222/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm321271.htm |url-status=dead }}

After a manufacturer's appeal Regorafenib was restored to the list of treatments funded by the English Cancer Drugs Fund.{{cite news|title=Cancer fund reprieve for just one drug, Regorafenib|url=https://www.bbc.co.uk/news/health-32835516|access-date=June 7, 2015|publisher=BBC|date=May 22, 2015|archive-date=May 26, 2015|archive-url=https://web.archive.org/web/20150526003604/http://www.bbc.co.uk/news/health-32835516|url-status=live}}

In February 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.{{cite news |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340958.htm |title=FDA approves Stivarga for advanced gastrointestinal stromal tumors |date=February 25, 2013 |access-date=August 30, 2024 |archive-date=January 18, 2017 |archive-url=https://web.archive.org/web/20170118093056/http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm340958.htm |url-status=dead }}

In November 2018, the National Institute for Health and Care Excellence (NICE) approved use of regorafenib in people with advanced hepatocellular carcinoma who were previously treated with sorafenib.{{cite news|url=https://www.nice.org.uk/news/article/life-extending-treatment-for-patients-with-advanced-liver-cancer-recommended-by-nice|title=Life extending treatment for patients with advanced liver cancer recommended by NICE|date=November 29, 2018|access-date=August 30, 2024|archive-date=November 29, 2018|archive-url=https://web.archive.org/web/20181129140314/https://www.nice.org.uk/news/article/life-extending-treatment-for-patients-with-advanced-liver-cancer-recommended-by-nice|url-status=dead}}

MetastaticCRC: After the CORRECT trial, two phase 3 trials (CONSIGN, CONCUR) showed benefits compared to placebo. Regorafenib dosing was 150 or 160 mg/d for first 3 weeks of each 4 week cycle.{{Cite web |url=http://www.cancernetwork.com/esmo-2015-world-gi/consign-concur-confirm-efficacy-regorafenib-mcrc |title=CONSIGN, CONCUR Confirm Efficacy of Regorafenib in mCRC. 2015 |access-date=July 29, 2015 |archive-date=July 15, 2017 |archive-url=https://web.archive.org/web/20170715012737/http://www.cancernetwork.com/esmo-2015-world-gi/consign-concur-confirm-efficacy-regorafenib-mcrc |url-status=live }}

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 (mucositis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia).{{cite web | title=FDA Prescribing Information | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203085lbl.pdf | date=September 27, 2012 | access-date=September 27, 2012 | archive-date=December 2, 2020 | archive-url=https://web.archive.org/web/20201202104116/https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203085lbl.pdf | url-status=live }}

Regorafenib and at least one of its analogs, sorafenib, are potent inhibitors of Soluble epoxide hydrolase (sEH).{{cite journal | vauthors = Zhang G, Kodani S, Hammock BD | title = Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer | journal = Progress in Lipid Research | volume = 53 | pages = 108–23 | date = January 2014 | pmid = 24345640 | pmc = 3914417 | doi = 10.1016/j.plipres.2013.11.003 }} sEH metabolizes, and in general thereby inactivates, epoxyeicosatrienoic acids (EETs), epoxydocosapentaenoic acids (EDPs), epoxyeicosatetraenoic acids (EEQs), and other epoxy polyunsaturated fatty acids that are made by various cytochrome P450 epoxygenases. EETs, EDPs, and EEQs have various effects in animals including vasodilation, anti-hypertensive, and anti-blood-clotting actions. However, EDPs, unlike EETs, inhibit the vascularization, growth, and metastasis of human cancer cells in vitro and in animal models. It is suggested that the inhibition of sEH and consequential increase in EDP levels contributes to the anti-cancer activity of regorafenib and related analogs,{{cite journal | vauthors = Hwang SH, Wecksler AT, Zhang G, Morisseau C, Nguyen LV, Fu SH, Hammock BD | title = Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH inhibitors | journal = Bioorganic & Medicinal Chemistry Letters | volume = 23 | issue = 13 | pages = 3732–7 | date = July 2013 | pmid = 23726028 | pmc = 3744640 | doi = 10.1016/j.bmcl.2013.05.011 }} a possibility supported by studies showing that 1) DHA acted synergistically with regorafenib to increase EDP levels in and inhibit the growth of several human renal cancer cell lines in vitro and 2) dietary DHA likewise acted synergistically with regorafenib to inhibit the invasiveness and growth of a human renal cancer cell line while increasing its EPA levels in mice.{{cite journal | vauthors = Kim J, Ulu A, Wan D, Yang J, Hammock BD, Weiss RH | title = Addition of DHA Synergistically Enhances the Efficacy of Regorafenib for Kidney Cancer Therapy | journal = Molecular Cancer Therapeutics | volume = 15 | issue = 5 | pages = 890–8 | date = May 2016 | pmid = 26921392 | pmc = 4873345 | doi = 10.1158/1535-7163.MCT-15-0847 }} These preclinical studies suggest that dietary supplementation with omega-3 fatty acids, particularly DHA, may be useful in enhancing the anti-cancer actions of regorafenib in humans.

In Bangladesh under the trade name Regonix.{{medcn|date=March 2020}}, Regora manufactured by Beacon Pharmaceuticals Ltd.

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