Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group

J Clin Oncol. 2015 Aug 1;33(22):2444-9. doi: 10.1200/JCO.2014.60.4587. Epub 2015 Jun 29.

Abstract

Purpose: Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine.

Patients and methods: Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses.

Results: A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment.

Conclusion: This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.

Trial registration: ClinicalTrials.gov NCT01626781.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antioxidants / administration & dosage*
  • Breast Neoplasms / drug therapy
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives*
  • Gastrointestinal Neoplasms / drug therapy
  • Germany
  • Hand-Foot Syndrome / etiology
  • Hand-Foot Syndrome / pathology
  • Hand-Foot Syndrome / prevention & control*
  • Humans
  • Incidence
  • Keratolytic Agents / administration & dosage*
  • Male
  • Middle Aged
  • Ointments
  • Primary Prevention / methods*
  • Quality of Life*
  • Severity of Illness Index
  • Skin Cream
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Failure
  • Urea / administration & dosage*

Substances

  • Antimetabolites, Antineoplastic
  • Antioxidants
  • Keratolytic Agents
  • Ointments
  • Deoxycytidine
  • Capecitabine
  • Urea
  • Fluorouracil

Associated data

  • ClinicalTrials.gov/NCT01626781