Hand-foot syndrome prevention: pharmacological interventions-systematic review and network meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Topical diclofenac RR 0.26 (74% risk reduction), Celecoxib RR 0.46 (54% risk reduction)

• Primary Outcome: Incidence of moderate to severe HFS (grade 2-3)

• Nnt Or Sensitivity: Based on RR 0.26 for diclofenac, estimated NNT approximately 3-4 patients (assuming baseline risk 20-30%)

• Confidence Interval: Diclofenac 95% CI 0.10-0.66, Celecoxib 95% CI 0.26-0.84

Clinical Application

Topical diclofenac is readily available, cost-effective, and easy to apply with minimal systemic absorption Diclofenac gel is PBS-listed for musculoskeletal conditions; off-label use for HFS prevention would require clinical judgment and patient consent. Aligns with supportive care guidelines from Cancer Australia Cancer patients receiving capecitabine or other HFS-associated chemotherapy regimens

Abstract

INTRODUCTION: Hand-foot syndrome (HFS) is a dermatological side effect of chemotherapies such as capecitabine and pegylated liposomal doxorubicin. Over recent years, numerous randomised controlled trials (RCTs) have investigated various pharmacological strategies to prevent HFS. Although urea cream and celecoxib have shown promising results, the efficacy of topical diclofenac remains unclear. To provide a comprehensive comparison of pharmacological interventions for HFS prevention in cancer patients undergoing chemotherapy, we conducted a network meta-analysis (NMA). METHODS: We systematically searched PubMed, Cochrane and Scopus for relevant RCTs published up to November 2024. The primary outcome was the incidence of moderate to severe HFS (grade 2-3), while secondary outcomes included the occurrence of all-grade HFS (grade≥1) and chemotherapy modifications. Risk ratios (RR) with 95% CIs were estimated for all outcomes using NMA. RESULTS: Thirteen RCTs comprising 1983 patients, most of whom received capecitabine (n=1849) were included, evaluating five pharmacological interventions. Both topical diclofenac (RR 0.26, 95% CI 0.10 to 0.66) and celecoxib (RR 0.46, 95% CI 0.26 to 0.84) significantly reduced the risk of moderate to severe HFS compared with placebo. Notably, topical diclofenac was the only intervention that significantly reduced the incidence of all-grade HFS and the need for chemotherapy modifications. CONCLUSION: Our NMA demonstrates that topical diclofenac provides the most robust protective effect among available pharmacological interventions for HFS prevention and is also associated with fewer chemotherapy modifications. These findings support its consideration as a preferred preventative strategy for patients at risk of HFS during chemotherapy. PROSPERO REGISTRATION NUMBER: CRD42025643635.

References

1. 1.Saeteaw, M., Thippharak, T., Porasuntisuk, K., Kengkla, K., Chan, A., & Subongkot, S. (2026). Hand-foot syndrome prevention: pharmacological interventions-systematic review and network meta-analysis. BMJ Supportive & Palliative Care. https://doi.org/10.1136/spcare-2025-005639