Prophylactic Medium-Class Topical Steroids are Associated with a Lower Incidence of Capecitabine-Induced Hand-Foot Syndrome in Patients with Colorectal Cancer

There is limited clinical research evaluating the role of topical corticosteroids in preventing hand-foot syndrome (HFS) caused by capecitabine. Although the precise cause of HFS remains unclear, inflammatory mechanisms are thought to contribute to its development. This study investigated whether prophylactic use of a medium-class topical corticosteroid was associated with a lower incidence of capecitabine-related HFS in patients with colorectal cancer. We retrospectively assessed 78 patients prescribed medium-class topical steroids as a preventive against HFS associated with capecitabine and 32 topical steroid-free patients undergoing capecitabine-based chemotherapy. We evaluated the incidence of each grade of HFS during chemotherapy. Between January 2022 and March 2025, 110 patients were enrolled in the study. Grade ≥ 2 HFS occurred in 23.1% of patients in the medium-class topical steroid group and 50.0% of patients in the topical steroid-free group (OR, 0.30; 95% CI 0.13–0.72; P = 0.012, Fisher’s exact test). The incidence of other capecitabine-related adverse events did not differ significantly between the groups. Our findings suggest that prophylactic use of medium-class topical steroids was associated with a lower incidence of capecitabine-induced hand-foot syndrome. Prospective randomized studies are warranted to confirm these findings. Hand-foot syndrome is a common side effect of capecitabine chemotherapy that can cause pain, redness, and difficulty using the hands and feet. Severe symptoms often lead to dose reductions or treatment discontinuation. In this retrospective, nonrandomized study, patients who applied a medium-class (mid-strength) topical steroid cream to their hands and feet from the start of chemotherapy developed hand-foot syndrome less frequently than patients who did not use topical steroids. No steroid-related side effects were observed. These findings suggest that prophylactic use of a medium-class (mid-strength) topical steroid cream may be associated with a lower incidence of capecitabine-induced hand-foot syndrome.