Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis

• Published in: Investigational new drugs 2013-08, Vol.31 (4), p.1078-1086
• Main Authors: Belum, Viswanath Reddy, Wu, Shenhong, Lacouture, Mario E.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cancer therapies; Chemotherapy; Clinical outcomes; Clinical trials; Clinical Trials as Topic; Colorectal cancer; Dermatology; Drug dosages; Drug therapy; Drug toxicity and drugs side effects treatment; Drugs; Gastrointestinal cancer; Hand-Foot Syndrome - epidemiology; Hand-Foot Syndrome - pathology; Humans; Hypertension; Incidence; Kinases; Liver cancer; Medical sciences; Medicine; Medicine & Public Health; Meta-analysis; Metastasis; Neoplasms - drug therapy; Oncology; Pharmaceutical sciences; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyridines - adverse effects; Pyridines - therapeutic use; Review; Risk Factors; Skin - drug effects; Skin - pathology; Statistical analysis; Studies; Toxicity; Toxicity: skin, dermoskeleton; Tumors; Vascular disorders of the skin
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-013-9977-0

Summary Background Regorafenib is a novel receptor tyrosine kinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). The drug targets multiple receptors, including VEGF-R1/-R2/-R3, TIE-2, FGFR-1, PDGFR-α/β, KIT, RET, RAF, p38 MAPK. Adverse events include asthenia, hypertension, diarrhea, and hand-foot skin reaction (HFSR), with the latter representing one of the most clinically significant untoward events. The incidence and risk of HFSR with regorafenib have not been systematically investigated. Methods We conducted a meta-analysis to ascertain the incidence and risk of developing HFSR in cancer patients treated with regorafenib. Electronic databases (PubMed, Scopus, Web of Science) and the ASCO website were searched for publications from January 1998–January 2013. Eligible studies were limited to Phase II/III clinical trials employing regorafenib (160 mg/day). The incidence, relative risk (RR), and 95 % CIs were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results A total of 1,078 patients treated with regorafenib for mCRC, GIST, renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) were included. The overall incidence of all-grade and high-grade HFSR were 60.5 % (95 % CI: 48.3–71.6 %) and 20.4 % (95 % CI: 15.4–26.6 %), respectively. The RRs of all-grade and high-grade HFSR with regorafenib in comparison to controls were increased for all-grade (RR = 5.4, 95 % CI: 3.76–7.76, p