title: The safety of regorafenib for the treatment of gastrointestinal stromal tumors.
abstract: BACKGROUND
  The management of gastrointestinal stromal tumors (GIST) evolved due to effective molecularly targeted therapy with imatinib and sunitinib which are used first- and second-line, respectively. However, due to the development of resistance to those drugs in the majority of patients, the need for third-line therapy arose.
  
  
  METHODS
  Regorafenib, an oral multitargeted inhibitor with activity against multiple kinases including KIT, RET, RAF1, BRAF, angiogenesis (VEGFR, TIE-2) and those involved in tumor microenvironment (PDGFR and FGFR) was introduced after the successful Phase III GRID (GIST - Regorafenib In progressive Disease) clinical trial. This study showed significant improvement in progression-free survival for patients receiving regorafenib compared to placebo (4.8 months vs 0.9 months). The treatment was reasonably well tolerated, with arterial hypertension, hand-foot syndrome, diarrhea being the most common grade ≥3 adverse events, which could be managed by dose reduction and supportive treatment. The aim of this paper is to describe, assess and advise on the safety of regorafenib as third-line therapy in GIST.
  
  
  CONCLUSIONS
  Regorafenib has demonstrated clinical benefit in GIST patients after progression on prior treatment with at least imatinib/sunitinib and currently it is the approved standard third-line option in therapy of advanced GIST. The safety profile is similar to other multikinase inhibitors with anti-VEGFR activity and is manageable.
authors.affiliation: a Department of Soft Tissue/Bone Sarcoma and Melanoma , Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw 02-781 , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.affiliation: a Department of Soft Tissue/Bone Sarcoma and Melanoma , Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw 02-781 , Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stępniak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib
keywords: GIST; adverse event; gastrointestinal stromal tumors; imatinib; regorafenib; sunitinib; tyrosine kinase inhibitor