Evaluation of a urea/lactic acid-based topical keratolytic agent (ULABTKA) for prevention of capecitabine-induced hand and foot syndrome (HFS): NCCTG trial N05C5.

Abstract

9017 Background: HFS is a dose-limiting toxicity of capecitabine, occurring in 43-71% of patients. No effective preventative treatment has been definitively demonstrated. Urea/lactic acid have hydrating and keratolytic properties. Pilot data suggest that they may prevent HFS. The purpose of this trial was to evaluate the prophylactic use of a ULABTKA for capecitabine-induced HFS. Methods: A randomized double-blind phase III trial evaluated 137 patients (pts) receiving their first ever cycle of capecitabine at a dose of either 2,000 or 2,500 mg/m2 per day for 14 days. Pts were randomized to a ULABTKA vs. a placebo cream, which was applied to the hands and feet BID for 21 days after the start of capecitabine. Pts completed a HFS Diary (HFSD) daily while applying the cream. HFS toxicity grade (CTCAE v 3.0) was also collected at baseline and at the end of each cycle. The primary endpoint was assessed by comparing the percentage of pts in each group who self-reported moderate severity (or worse) HFS during cycle 1 as measured by the HFSD. The planned 132 pts provided 80% power for detecting a moderate effect size of 18% difference with a two-sided Fisher's exact test at a 5% Type I significance level. Results: The percentage of pts with moderate or severe HFS was not different between the two arms, with 13.6% in the ULABTKA arm and 10.2% in the placebo arm (p % 0.768, using a Fisher's exact test). Maximum HFS severity frequency data and chi-square p-values from this cycle 1 are illustrated in the Table. Cycle 1 CTCAE skin toxicity was higher in the ULABTKA arm, but not significantly so (p % 0.82). No significant differences were observed in other toxicities between the two arms. Conclusions: These data do not support the efficacy of a ULABTKA cream for preventing symptoms of HFS in patients receiving capecitabine. HFS severity Location Hands Feet Combined (hands and feet) Urea Placebo Urea Placebo Urea Placebo None 35 (59%) 36 (74%) 38 (64%) 34 (69%) 32 (54%) 31 (63%) Mild 18 (31%) 11 (22%) 14 (24%) 10 (20%) 19 (32%) 13 (27%) Moderate 5 (9%) 1 (2%) 6 (10%) 3 (6%) 6 (10%) 3 (6%) Severe 1 (2%) 1 (2%) 1 (2%) 2 (4%) 2 (3%) 2 (4%) P value 0.324 0.727 0.747 No significant financial relationships to disclose.