A randomized controlled phase II study of the prophylactic effect of urea-based cream on the hand-foot skin reaction associated with sorafenib in advanced hepatocellular carcinoma.

Abstract

4008 Background: Sorafenib (SOR) has become the standard treatment for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is one of the most common adverse events associated with SOR and its occurrence can impact patient quality of life and lead to dose modification or interruption, both of which may negatively impact clinical outcomes. This randomized controlled trial is the first large prospective study to investigate the prophylactic effect of urea-based creams on HFSR associated with SOR. Methods: Patients with advanced HCC treated with SOR were randomly assigned 1:1 to receive prophylactic urea-based cream (Arm A) or best supportive care (BSC) following development of HFSR (Arm B). SOR was administered 800 mg daily. Urea-based cream was given twice daily for up to 12 weeks starting on Day 1. BSC was at the physician’s discretion and excluded urea-based creams. The primary endpoint was the incidence of all-grade HFSR in the first12 weeks. Results: Eight hundred sixty eight patients were enrolled; 439 patients in Arm A and 432 patients in Arm B. There was no difference of baseline characteristics between two arms. Over the 12 week period of study, the incidence of all-grade HFSR was significantly lower in Arm A compared to Arm B; n=246 (56.0%) patients in Arm A versus n=318 (73.6%) patients in Arm B, p<0.0001. The incidence of grade ≥2 HFSR tended to be lower in Arm A compared to Arm B, but did not reach statistical significance; n=96 (21.9%) patients Arm A versus n=126 (29.2%) patients in Arm B, p=0.1638. The median time to the first HFSR event was 2.5 fold longer in Arm A compared to Arm B; 84 days (95% CI 45-93 days) in Arm A and 34 days (95% CI 29-43 days) in Arm B (p<0.001). Conclusions: This is the first large prospective, randomized control trial examining the prophylactic use of urea-based creams for treatment of HFSR associated with a multikinase inhibitor. Compared to BSC, prophylactic topical use of a urea-based cream appears to be effective in preventing and/or delaying the incidence of HFSR associated with SOR treatment in patients with advanced HCC.