title: Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care.
abstract: Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies. The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary.
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy grothey.axel@mayo.edu suzanne_george@dfci.harvard.edu.
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy grothey.axel@mayo.edu suzanne_george@dfci.harvard.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy.
authors.forename: Eric
authors.initials: E
authors.lastname: van Cutsem
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sobrero
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Léon Bérard Centre and Claude Bernard University, Lyon, France; IRCCS San Martino, Genoa, Italy.
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
mesh_terms: D018572:Disease-Free Survival; D054796:Drug Dosage Calculations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D060831:Hand-Foot Syndrome / Q000473:pathology; D006801:Humans; D010361:Patients; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib
keywords: Adverse events; Dose optimization; Hand-foot skin reaction; Multikinase inhibitor; Regorafenib; Supportive management