Topical Delgocitinib for Capecitabine-Induced Hand–Foot Syndrome: A Therapeutic Option?

Hand–foot syndrome (HFS) is a frequent and potentially dose-limiting adverse event of capecitabine. Current therapeutic strategies are not always effective. Since inflammatory pathways, including JAK-STAT3 signaling, may contribute to capecitabine-induced HFS, topical JAK inhibition could represent a potential therapeutic approach. We report two women with metastatic breast cancer receiving capecitabine monotherapy who developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 HFS involving both palms and soles. Both patients had previously received clobetasol propionate 0.05% combined with urea 30%, with only transient benefit. Delgocitinib 20 mg/g cream was subsequently applied twice daily to palms and soles for 6 weeks. Treatment response was assessed clinically and using the HFS-14 quality-of-life scale. Capecitabine dose and schedule remained unchanged in both patients throughout the 6-week delgocitinib treatment period. In patient 1, HFS improved from CTCAE grade 3 to grade 1, with marked symptomatic improvement and a decrease in HFS-14 score from 73.5 to 17.6. Capecitabine was continued unchanged, and the clinical improvement remained stable during an additional 3 months of follow-up. In patient 2, erythema decreased, but desquamation and burning persisted; HFS remained CTCAE grade 3 and the HFS-14 score decreased from 76.5 to 67.6. Capecitabine was therefore interrupted after the week 6 assessment. No local or systemic adverse events related to delgocitinib were observed. Topical delgocitinib may represent a potential therapeutic strategy for capecitabine-induced HFS, particularly in patients who do not adequately respond to topical corticosteroid therapy. However, the discordant responses observed in these two cases highlight that its therapeutic role remains uncertain and requires further prospective investigation.