Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Abstract

Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine-induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3weeks during these 9weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9th week (p<0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine-induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.