title: Possible Pathways of Capecitabine-Induced Hand-Foot Syndrome.
abstract: Capecitabine, an oral prodrug of 5-fluorouracil, inhibits DNA synthesis and has received FDA approval for treatment of metastatic colorectal and breast cancers. Hand-foot syndrome (HFS) is a serious dose-limiting toxicity and the most frequently reported side effect of capecitabine. Because of the lack of knowledge about the causative mechanism of HFS, scarce information is available for effective treatment or prevention. Data are based on published literatures and reports available from the HFS development program database. The purpose of this Review is to provide information regarding definition, clinical manifestation, and the possible mechanisms of HFS induced by capecitabine. Ethnic variations in the clinical presentation of HFS warrant further attention. Several physiological and pharmacological mechanisms have been investigated, such as cyclooxygenase (COX) inflammatory-type reaction, accumulation of capecitabine metabolites, and enzymes and transporters involved in the metabolism and absorption. Although current studies describe the possible mechanisms of HFS induced by capecitabine, much remains to be determined. It appears from this scientific evidence that additional study is needed to determine the effect of skin-mediated metabolism in the possible mechanism of HFS induced by capecitabine.
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University , 79 QingChun Road, Hangzhou, Zhejiang 310000, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lou
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University , 79 QingChun Road, Hangzhou, Zhejiang 310000, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Zhejiang Institute for Food and Drug Control , Hangzhou, Zhejiang 310004, People's Republic of China.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou, Zhejiang 310058, People's Republic of China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University , 79 QingChun Road, Hangzhou, Zhejiang 310000, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University , 79 QingChun Road, Hangzhou, Zhejiang 310000, People's Republic of China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hong
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou, Zhejiang 310058, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000069287:Capecitabine / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology* / Q000378:metabolism*; D006801:Humans
chemical_list: D000964:Antimetabolites, Antineoplastic; D000069287:Capecitabine