Diclofenac, Silymarin Show Promise for Preventing Chemotherapy-Induced Hand-Foot Syndrome: Meta-analysis
Key Takeaways
A new network meta-analysis of 19 randomized clinical trials indicated several efficacious pharmacologic prevention strategies for chemotherapy-induced hand-foot syndrome (HFS).
Diclofenac, topical silymarin, celecoxib, and 400-mg pyridoxine reduced the incidence of grade 2 or higher HFS vs. placebo.
Diclofenac showed the most consistent evidence across outcomes and study quality; silymarin ranked highest in efficacy but requires confirmation in larger trials, according to the authors.
Diclofenac and topical silymarin reduced the risk of grade 2 or higher chemotherapy-induced hand-foot syndrome (HFS), according to a new meta-analysis of randomized clinical trials evaluating pharmacologic preventive strategies.
Investigators for the systematic review searched PubMed, Embase, and Cochrane CENTRAL from database inception through November 2024 to identify phase 2 or 3 randomized clinical trials evaluating systemic or topical prophylactic interventions for HFS. Nineteen trials met inclusion criteria. Seventeen trials including 2,192 patients (median age, 57 years) were included in the primary analysis evaluating grade 2 or higher HFS. The primary endpoint was incidence of grade 2 or higher HFS, with a secondary endpoint of any-grade HFS incidence.
Several interventions were observed to reduce the risk of grade 2 or higher HFS, according to the results. Topical silymarin demonstrated the greatest relative reduction (OR = 0.08; 95% CI, 0.01 to 0.71), followed by diclofenac (OR = 0.23; 95% CI, 0.08 to 0.62), pyridoxine 400 mg (OR = 0.28; 95% CI, 0.09 to 0.88), and celecoxib (OR = 0.41; 95% CI, 0.18 to 0.95). Diclofenac (OR = 0.30; 95% CI, 0.13 to 0.69) and celecoxib (OR = 0.46; 95% CI, 0.22 to 0.94) also significantly reduced the incidence of HFS of any grade. In contrast, silymarin and pyridoxine did not significantly affect overall HFS incidence, while mapisal was associated with increased risk (OR = 3.04; 95% CI, 1.07 to 8.64).
Ranking analyses showed the highest SUCRA values for silymarin (0.91) and diclofenac (0.76).
“In this systematic review and network meta-analysis, diclofenac and silymarin were the most effective preventive strategies for HFS, with silymarin requiring confirmation in a larger randomized trial,” the authors wrote. “Diclofenac emerged as the agent with the best overall supporting evidence, informed by both effect estimates and study quality.”
Source: Baskarain H, et al. JAMA Dermatology. 2026. Doi:10.1001/jamadermatol.2026.0042