Topical diclofenac and silymarin were associated with a reduced risk of clinically significant hand-foot syndrome in patients receiving chemotherapy, according to a systematic review and network meta-analysis published online in JAMA Dermatology.
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a dose-dependent cutaneous toxic effect most commonly seen with capecitabine and other fluoropyrimidines. It presents with erythema, edema, and dysesthesia of the palms and soles and may progress to blistering or ulceration. Although not life-threatening, grade 2 or higher HFS can interfere with daily activities and often leads to dose reduction or treatment interruption.
Researchers at the All India Institute of Medical Sciences, New Delhi, evaluated pharmacologic strategies for preventing chemotherapy-induced HFS, searching PubMed, Embase, and Cochrane CENTRAL through November 2024 and identified 19 phase 2 or 3 randomized clinical trials. Seventeen trials including 2,192 patients were analyzed for the primary outcome of grade 2 or higher HFS.
Most studies involved capecitabine-treated patients with breast, colorectal, gastrointestinal, or ovarian cancers, as well as multiple myeloma. Thirteen prophylactic interventions were assessed, including topical and systemic agents.
Compared with placebo, four interventions were associated with a statistically significant reduction in grade 2 or higher HFS: topical silymarin, diclofenac gel, pyridoxine (400 mg), and celecoxib. Diclofenac and celecoxib were also associated with reduced overall HFS incidence (any grade). Silymarin and high-dose pyridoxine did not significantly reduce overall HFS, and mapisal cream was associated with an increased risk.
In treatment ranking analyses using surface under the cumulative ranking curve (SUCRA) values, silymarin ranked highest, followed by diclofenac. However, the silymarin findings were based on a small phase 2 trial of 40 patients. Diclofenac was supported by a larger phase 3 trial that included 263 patients.
Across the network, heterogeneity was low and no significant inconsistency was detected. Most trials were assessed as having low to moderate risk of bias.
The authors noted that several interventions were evaluated in relatively small studies and that HFS grading systems varied across trials. In addition, all four interventions associated with reduced grade 2 or higher HFS were studied in Asian populations, which may limit generalizability. Most included trials focused on capecitabine, and it remains unclear whether similar preventive effects apply to other chemotherapeutic agents.
The researchers concluded that diclofenac had the most consistent supporting evidence among evaluated strategies and stated that larger randomized trials are needed to confirm the findings for silymarin.
Source: JAMA Dermatology.
