Abstract
Regorafenib (Stivarga, BAY 73-4506; Bayer Pharma AG, Berlin, Germany) is an oral multikinase inhibitor that targets the angiogenic tumor microenvironment and oncogenic kinases including vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR1, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), RAF, KIT, RET and BRAF. Its antiangiogenic effect is greater than that of its related drug, sorafenib. Regorafenib has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (mCRC) in patients who have failed treatment with fluoropyrimidine, oxaliplatin and irinotecan based chemotherapy, an anti-VEGF therapy and, if KRAS wild type, an anti-EGFR therapy. The FDA based this approval on data from the CORRECT trial, which showed the efficacy of regorafenib compared with placebo. The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension and fatigue. This review discusses the efficacy data, and the incidence and management of regorafenib's toxicities.
References
Feb 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·K MaedaY Arimoto
Dec 1, 1995·Annals of Surgery·R E FrankD B Rubin
Sep 23, 1997·Scandinavian Journal of Gastroenterology·S J Lewis, K W Heaton
Nov 13, 2001·American Journal of Clinical Dermatology·E NagoreO Sanmartín
Apr 27, 2004·Cancer·Stephen T SonisUNKNOWN International Society for Oral Oncology
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Feb 8, 2005·Seminars in Oncology·Lee M Ellis
Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
May 5, 2005·British Journal of Cancer·A AwadaM Piccart
Oct 4, 2006·Nature Reviews. Drug Discovery·Scott WilhelmSusan Kelley
Aug 1, 2007·The Oncologist·Jennifer K CarrollGary R Morrow
Sep 16, 2010·Nature Reviews. Cardiology·Michael S Ewer, Steven M Ewer
Dec 21, 2010·International Journal of Cancer. Journal International Du Cancer·Scott M WilhelmDieter Zopf
Mar 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Klaus MrossOlaf Christensen
May 10, 2012·British Journal of Cancer·D StrumbergK Mross
Sep 14, 2012·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·A E Bennion, A Molassiotis
Sep 18, 2012·International Journal of Colorectal Disease·Thomas C WehlerCarl C Schimanski
Nov 28, 2012·Lancet·Axel GrotheyUNKNOWN CORRECT Study Group
Nov 28, 2012·Lancet·George D DemetriUNKNOWN GRID study investigators
Nov 28, 2012·Lancet·Tom Waddell, David Cunningham
Jan 26, 2013·Journal of Clinical Epidemiology·Morten Aa PetersenUNKNOWN EORTC Quality of Life Group
Mar 16, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B SchultheisK B Mross
Apr 27, 2013·Molecular Cancer Therapeutics·Lotfi Abou-ElkacemWiltrud Lederle
Sep 3, 2013·Current Treatment Options in Oncology·Viswanath Reddy BelumMario E Lacouture
Oct 8, 2013·PloS One·Clemens C CyranKonstantin Nikolaou
Oct 22, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Josep TaberneroCarmen J Allegra
Oct 24, 2013·European Journal of Clinical Pharmacology·Zexing WangXiaoxiang Guan
Dec 7, 2013·Current Oncology·B GagnonN Macdonald
May 7, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kathryn J RuddyCharles L Loprinzi
May 14, 2014·The Oncologist·Axel GrotheyGeorge D Demetri
Jul 17, 2014·Critical Reviews in Oncology/hematology·Omar Abdel-Rahman, Mona Fouad
Sep 17, 2014·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J SastreC Pericay
Citations
Sep 2, 2016·Biochimica Et Biophysica Acta·Ivan HaralampievPeter Müller
Oct 27, 2016·Future Oncology·Salvatore Del PreteRaffaele Addeo
Apr 6, 2017·Scientific Reports·Riccardo GiampieriMario Scartozzi
Oct 3, 2017·Case Reports in Oncology·Dominique BéchadeMarianne Fonck
Sep 25, 2017·Investigational New Drugs·Meihui CaoJingdong Zhang
Aug 25, 2019·Cancers·Yoshitaro ShindoHiroaki Nagano
Oct 20, 2017·Medicine·Kenji TsuchihashiEishi Baba
Dec 22, 2017·Oncotarget·Zhenghu ChenJianhua Yang
Jul 9, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Diva SilvaIsabel F Almeida
Mar 13, 2020·International Journal of Cancer. Journal International Du Cancer·Sarun JuengpanichXiujun Cai
May 28, 2020·British Journal of Cancer·Divya SubramonianPeter E Zage
May 20, 2016·Journal of Lower Genital Tract Disease·Emma-Lee BourneJames Scurry
Mar 6, 2017·Oncology Reports·Nao KakizawaToshiki Rikiyama
Jun 19, 2019·Advances in Therapy·Ganfeng XieHoujie Liang
Sep 29, 2019·International Cancer Conference Journal·Keita TashiroHideki Ueno
Oct 12, 2018·Hepatic Oncology·Francesco TovoliAlessandro Granito
Apr 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·N A SeebacherA M Merlot
Jan 9, 2020·Clinical Sarcoma Research·Florence ChamberlainCharlotte Benson
Oct 27, 2020·International Journal of Clinical Oncology·Yasushi MurachiTaroh Satoh
Mar 3, 2021·Drugs & Aging·Monika Dudzisz-ŚledźPiotr Rutkowski
Jan 5, 2021·JHEP Reports : Innovation in Hepatology·Masatoshi KudoAndrew X Zhu
Apr 6, 2021·Current Hepatology Reports·Adeniji Nia, Renumathy Dhanasekaran
Jul 1, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Erwin WoffPatrick Flamen
May 24, 2021·Bioorganic Chemistry·Mohammed M AlanaziIbrahim H Eissa
Jul 3, 2021·Pharmaceuticals·Julie BolcaenCharlot Vandevoorde
Jun 13, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·N A Bhaskaran, L Kumar
Jul 31, 2021·World Journal of Gastroenterology : WJG·Hsuan YehTzung-Hai Yen
Jul 22, 2021·Cancer Management and Research·Ralf-Dieter HofheinzDawn Odom
Sep 9, 2021·ACS Applied Materials & Interfaces·Seounghun KangHongje Jang
Oct 9, 2021·Journal of Cutaneous Pathology·Riyad N H SeervaiJonathan L Curry
Nov 27, 2021·Journal of Palliative Care·Hiroshi HamadaHiroyuki Uchino