Topical Diclofenac for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Prospective Real-World Study.

Abstract

Capecitabine-induced hand-foot syndrome (HFS) is a frequent toxicity that impairs quality of life and may require chemotherapy dose modification. Although prophylactic topical diclofenac showed benefit in a randomized trial, its effectiveness in routine clinical practice remains uncertain. We evaluated the real-world effectiveness of topical diclofenac for prevention of clinically significant capecitabine-induced HFS. DICLO-HFS was a prospective, two-center observational study conducted in Türkiye between July 2023 and February 2024. Adults with colorectal or gastric cancer receiving capecitabine-based therapy were managed with either prophylactic 1% topical diclofenac twice daily or active monitoring according to routine practice. HFS was assessed weekly using Common Terminology Criteria for Adverse Events v5.0 by physicians not involved in treatment allocation. The primary end point was incidence of grade ≥2 HFS. Secondary end points included time to onset of grade ≥2 HFS and capecitabine dose reductions attributable to HFS. A total of 151 patients were included (71 diclofenac; 80 active monitoring). During a median follow-up of 19.1 weeks, grade ≥2 HFS occurred in 12 (16.9%) of 71 patients receiving diclofenac and 11 (13.8%) of 80 patients under active monitoring (odds ratio [OR], 1.28 [95% CI, 0.52 to 3.10]; <i>P</i> = .591). Time to onset did not differ between groups (log-rank <i>P</i> = .392). HFS-related dose reductions occurred in 24 (33.8%) of 71 and 20 (25.0%) of 80 patients, respectively (OR, 1.53 [95% CI, 0.76 to 3.10]; <i>P</i> = .235). In multivariable analysis, female sex and capecitabine monotherapy were independently associated with grade ≥2 HFS. In this prospective real-world study, prophylactic topical diclofenac did not reduce clinically significant capecitabine-induced HFS or delay its onset compared with active monitoring. These findings do not support routine diclofenac prophylaxis in everyday practice.