Management of hand-foot syndrome induced by capecitabine

Capecitabine (Xeloda) is a systemic prodrug of 5-fluorouracil (5-FU), which is administered in an oral formulation. Hand-foot syndrome (HFS) has proven to be a chronic dose-limiting toxicity of capecitabine, leading to significant morbidity in patients receiving this agent. The purpose of this review is to define the pathophysiology, risk factors, incidence and management of capecitabine-induced HFS.

Literature for this review article was collected from the following databases: PubMed, CINAHL, and the proceedings of the American Society of Clinical Oncology (ASCO) confined to the years 1995-2006. The following key terms were used in the search: hand-foot syndrome, palmar-plantar erythrodysesthesia, capecitabine, Xeloda, colorectal cancer, and metastatic breast cancer.

HFS associated with capecitabine is a serious dose-limiting toxicity. Incidence of grade 3/4 toxicity is of extreme significance, and introduces the need for dose reductions and/or interruptions in capecitabine therapy. Drug-related therapies studied include topical emollients and creams, systemic and topical corticosteroids, nicotine patch, vitamin E, pyridoxine, and COX-2 inhibitors. However, due to the lack of randomized, controlled trials with these therapies, the current mainstay of treatment for the management of this toxicity is interruption of therapy and, if necessary, dose reduction.

Treatment interruption or dose reduction remain the only methods shown to effectively manage HFS, but supportive measures to reduce pain and discomfort and prevent secondary infection are very important. Many other prophylactic and treatment strategies have been investigated, with pyridoxine and COX-2 inhibitors being the most promising in case reports and retrospective studies; therefore, prospective, randomized, controlled trials are needed to prove their efficacy.