title: Critical appraisal of the use of regorafenib in the management of colorectal cancer.
abstract: The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I-II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients.
authors.affiliation: Division of Medical Oncology, Department of clinical and experimental medicine and surgery "F. Magrassi e A. Lanzara", Second University of Naples, Napoli, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Festino
authors.forename: Alessio
authors.initials: A
authors.lastname: Fabozzi
authors.forename: Anna
authors.initials: A
authors.lastname: Manzo
authors.forename: Valentina
authors.initials: V
authors.lastname: Gambardella
authors.forename: Erika
authors.initials: E
authors.lastname: Martinelli
authors.forename: Teresa
authors.initials: T
authors.lastname: Troiani
authors.forename: Ferdinando
authors.initials: F
authors.lastname: De Vita
authors.forename: Michele
authors.initials: M
authors.lastname: Orditura
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ciardiello
authors.forename: Floriana
authors.initials: F
authors.lastname: Morgillo
keywords: angiogenesis; colorectal cancer; regorafenib