Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5

J Clin Oncol. 2010 Dec 10;28(35):5182-7. doi: 10.1200/JCO.2010.31.1431. Epub 2010 Nov 8.


Purpose: Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine for which no effective preventative treatment has been definitively demonstrated. This trial was conducted on the basis of preliminary data that a urea/lactic acid-based topical keratolytic agent (ULABTKA) may prevent HFS.

Patients and methods: A randomized, double-blind phase III trial evaluated 137 patients receiving their first ever cycle of capecitabine at a dose of either 2,000 or 2,500 mg/m(2) per day for 14 days. Patients were randomly assigned to a ULABTKA versus a placebo cream, which was applied to the hands and feet twice per day for 21 days after the start of capecitabine. Patients completed an HFS diary (HFSD) daily. HFS toxicity grade (Common Terminology Criteria for Adverse Events [CTCAE] v3.0) was also collected at baseline and at the end of each cycle. The primary end point was the incidence of moderate/severe HFS symptoms in the first treatment cycle, based on the patient-reported HFSD.

Results: The percentage of patients with moderate/severe HFS symptoms was not different between groups, being 13.6% in the ULABTKA arm and 10.2% in the placebo arm (P = .768 by Fisher's exact test). The odds ratio was 1.37 (95% CI, 0.37 to 5.76). Cycle 1 CTCAE skin toxicity was higher in the ULABTKA arm but not significantly so (33% v 27%; P = .82). No significant differences were observed in other toxicities between groups.

Conclusion: These data do not support the efficacy of a ULABTKA cream for preventing HFS symptoms in patients receiving capecitabine.

Trial registration: NCT00296036.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Antimetabolites, Antineoplastic / adverse effects
  • Capecitabine
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Foot Dermatoses / chemically induced
  • Foot Dermatoses / prevention & control*
  • Hand Dermatoses / chemically induced
  • Hand Dermatoses / prevention & control*
  • Humans
  • Keratolytic Agents / therapeutic use*
  • Lactic Acid / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Syndrome
  • Urea / therapeutic use*


  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Keratolytic Agents
  • Deoxycytidine
  • Lactic Acid
  • Capecitabine
  • Urea
  • Fluorouracil

Associated data


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