{"entity":{"id":"idea-upgrade-topical-diclofenac-during-capecitabine","kind":"idea","name":"Anti-inflammatory gel on the palms and soles from the first day of capecitabine","aka":[],"tldr":"Capecitabine often makes the hands and feet sore and peeling, and the usual answer is a lower dose. In one randomised trial, a cheap diclofenac gel rubbed on the palms cut moderate or worse hand-foot syndrome from 15 to under 4 per cent and halved dose cuts. A later study in routine care found no benefit, and a larger Japanese trial on palms and soles is under way.","summary":"The trial. In D-TORCH, a single-site phase 3 double-blind trial in India, 264 people starting capecitabine for breast or gastrointestinal cancer were randomised to topical diclofenac or placebo gel for 12 weeks. Grade 2 or 3 hand-foot syndrome occurred in 3.8 per cent with diclofenac against 15.0 per cent with placebo, and capecitabine dose reductions because of it in 3.8 against 13.5 per cent. The gel was applied to the palms only.\n\nThe pooled evidence. A 2026 network meta-analysis of 13 trials (1983 patients, most on capecitabine) found topical diclofenac had the strongest effect on moderate to severe hand-foot syndrome (risk ratio 0.26) and was the only intervention that reduced chemotherapy modifications.\n\nThe doubt. In DICLO-HFS, a prospective observational study of 151 people in two Turkish centres, routine 1 per cent diclofenac gel did not reduce grade 2 or worse hand-foot syndrome against active monitoring (16.9 against 13.8 per cent). The Japanese J-DIRECT trial, a multicentre placebo-controlled phase 3 trial of diclofenac 0.1 per cent cream on palms and soles alongside standard prevention, was set up because D-TORCH did not test the soles and its control group had less hand-foot syndrome than earlier reports. How often diclofenac is offered with capecitabine has not been measured in any source read.","asOf":"2026-11-11","links":[{"label":"Santhosh et al., Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: a double-blind randomized controlled trial (J Clin Oncol 2024)","url":"https://doi.org/10.1200/jco.23.01730"},{"label":"Hand-foot syndrome prevention: pharmacological interventions, systematic review and network meta-analysis (BMJ Support Palliat Care 2026)","url":"https://doi.org/10.1136/spcare-2025-005639"},{"label":"Topical Diclofenac for Prevention of Capecitabine-Induced Hand-Foot Syndrome: a prospective real-world study (JCO Glob Oncol 2026)","url":"https://doi.org/10.1200/go-26-00151"},{"label":"Iimura et al., Phase III study of diclofenac cream for capecitabine-related hand-foot syndrome: study protocol of J-SUPPORT2401/JORTC-SUP06, J-DIRECT (Int J Clin Oncol 2025)","url":"https://doi.org/10.1007/s10147-025-02789-z"}],"tags":["protocol-upgrade","upgrade:promising","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["hand-foot-syndrome"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Diclofenac cream applied to the palms and soles twice daily from the first day of capecitabine reduces grade 2 or worse hand-foot syndrome within three months and the number of dose reductions it causes, against placebo cream with standard preventive care.","rationale":"Hand-foot syndrome is one of the commonest reasons capecitabine is reduced. Diclofenac acts on the local inflammation without the heart and stomach risks of oral celecoxib, costs little, and is already available everywhere.","test":"J-DIRECT, the multicentre randomised double-blind phase 3 trial of diclofenac cream against placebo cream, with grade 2 hand-foot syndrome within 3 months as the primary endpoint; a positive result would justify adding it to guideline prevention.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},"route":"/ideas/idea-upgrade-topical-diclofenac-during-capecitabine/","neighbours":{"section":[{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"}],"term":[{"id":"hand-foot-syndrome","kind":"term","name":"Hand-foot syndrome and hand-foot skin reaction","route":"/terms/hand-foot-syndrome/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"protocol":[{"id":"hand-foot-syndrome-prevention-and-dose-modification","kind":"protocol","name":"Hand-foot syndrome and hand-foot skin reaction: prevention, skin care and dose changes","route":"/protocols/hand-foot-syndrome-prevention-and-dose-modification/"}]}}