Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.
During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).
The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.
Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.
The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.