title: Regorafenib  for cancer.
abstract: BACKGROUND
  Regorafenib (BAY 73-4506) is a novel, orally active, diphenylurea multikinase inhibitor of VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF and p38 MAP kinase.
  
  
  METHODS
  This review covers the preclinical development of regorafenib as well as the pivotal Phase I studies. The safety profile of regorafenib is discussed in context with other oral multikinase inhibitors bearing a similar target profile. Current clinical developments, especially in colorectal cancer (CRC) and gastrointestinal stromal tumor (GIST), are addressed. Open questions on clinically useful biomarkers predicting response with regard to a personalized therapy strategy are also being discussed.
  
  
  CONCLUSIONS
  Regorafenib (BAY 73-4506) is a novel, orally active multikinase inhibitor that is well tolerated in preclinical mouse models as well as clinically according to Phase I - III trials performed. The toxicity profile is comparable with other oral multikinase inhibitors with similar molecular targets. Regorafenib has promising antineoplastic activity in various tumor types. Two large, randomized Phase III pivotal registration studies in patients with GIST and CRC, respectively, already completed enrolment, with final results being awaited. Further extensive clinical development as a single agent or in combination with standard chemotherapeutic agents in various malignant tumors is ongoing. Moreover, regorafenib has recently been granted Orphan Drug Status for GIST tumors and 'fast track' status for both GIST and CRC by the FDA.
authors.affiliation: University of Bochum, Marienhospital Herne, Department of Hematology and Medical Oncology, 40, 44625 Herne, Germany. dirk.strumberg@marienhospital-herne.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Strumberg
authors.forename: Beate
authors.initials: B
authors.lastname: Schultheis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017277:Drug Approval; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009965:Orphan Drug Production; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib