title: Sorafenib-associated hand-foot syndrome in Japanese patients.
abstract: Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis, having encouraging efficacy and tolerability in patients with metastatic renal cell carcinoma (RCC) and other tumors. However, hand-foot syndrome (HFS), a frequently reported adverse event under sorafenib treatment, sometimes causes interruption of the treatment or dose reduction. This study was conducted to review sorafenib-associated HSF in Japanese patients, to facilitate improvement of the management of HFS in clinical practice. We reviewed the combined results on HFS in three sorafenib studies in Japanese patients: (A) a phase II study of metastatic renal cell carcinoma; (B) a phase I study of solid tumor; and (C), phase I study of hepatocellular carcinoma. Severity of HFS was graded as 1-3 based on the modified grading scale of National Cancer Institute - Common Toxicity Criteria version 2.0 and Common Terminology Criteria for Adverse Events version 3.0. A total of 189 patients were included for analyses. The incidence of all-grade HFS was 51% (55% in A, 39% in B and 44% in C), and the incidence of grade 3 HFS was 7% (9% in A, 0% in B and 7% in C). Incidence of HFS seemed dose-dependent. These events were observed within 3-9 weeks after initiation of sorafenib treatment. The majority of HFS was manageable with symptomatic treatment and HFS caused permanent discontinuation of sorafenib in only one patient (in study A). The incidence of sorafenib-associated HFS is high compared to other adverse events. However, the present analyses showed that HFS under sorafenib treatment is well manageable in Japanese patients.
authors.affiliation: Department of Dermatology, Showa University School of Medicine Bayer Yakuhin Ltd, Osaka, Japan. miijima@med.showa-u.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Iijima
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukino
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Adachi
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Murai
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005533:Foot Dermatoses / Q000139:chemically induced*; D006229:Hand Dermatoses / Q000139:chemically induced*; D006801:Humans; D007564:Japan; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D000077157:Sorafenib; D013577:Syndrome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib