title: Regorafenib: a novel multitargeted tyrosine kinase inhibitor for colorectal cancer and gastrointestinal stromal tumors.
abstract: OBJECTIVE
  To review currently available literature on the oral multikinase inhibitor regorafenib and its role in the treatment of metastatic colorectal cancer (mCRC), and imatinib- and sunitinib-resistant gastrointestinal stromal tumors (GISTs).
  
  
  METHODS
  A comprehensive literature search was performed of PubMed/MEDLINE and American Society of Clinical Oncology (ASCO) abstracts (through August 2013).
  
  
  METHODS
  Preclinical pharmacological and phase I to III trials data analyzing regorafenib efficacy and safety in mCRC or imatinib- and sunitinib-resistant GIST patients were evaluated. All available English-language, peer-reviewed articles and ASCO abstracts with relevant information were reviewed.
  
  
  RESULTS
  Regorafenib was approved for mCRC in September 2012 and for imatinib- and sunitinib-resistant GISTs in February 2013. Regorafenib is an inhibitor of stromal, angiogenic, and oncogenic receptor tyrosine kinases, as well as the RAF/MEK/ERK signaling pathway. Phase III CORRECT (Regorafenib Monotherapy for Previously Treated Metastatic Colorectal Cancer) trial data demonstrated an overall survival benefit for mCRC patients treated with regorafenib (6.4 vs 5.0 months; P = .0052). Phase III GRID (Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib) trial data revealed a progression-free survival benefit in imatinib- and sunitinib-resistant GIST patients (4.8 vs 0.9 months; P < .0001). Its adverse event (AE) profile is comparable to that of other multikinase inhibitors. The most commonly observed grade ≥3 AEs included hypertension, hand-foot skin reaction, rash, diarrhea, and fatigue.
  
  
  CONCLUSIONS
  Regorafenib is a novel oral multikinase inhibitor that has shown promising results for patients with advanced, unresectable or metastatic treatment-refractory CRCs or imatinib- and sunitinib-resistant GISTs.
authors.affiliation: University of North Carolina (UNC) Eshelman School of Pharmacy, NC, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Crona
authors.forename: Meredith D
authors.initials: MD
authors.lastname: Keisler
authors.forename: Christine M
authors.initials: CM
authors.lastname: Walko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004347:Drug Interactions; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib
keywords: colorectal cancer; gastrointestinal stromal tumors; regorafenib