2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T907,Hand-foot syndrome (HFS) is a common dose-limiting toxic effect of several chemotherapy agents, particularly capecitabine. Despite its substantial impact on the patient's quality of life and potential to compromise therapeutic efficacy, effective preventive strategies remain limited. To evaluate and compare the efficacy of pharmacologic interventions for the prevention of chemotherapy-induced HFS through a network meta-analysis of published results of randomized clinical trials (RCTs). PubMed, Embase, and Cochrane CENTRAL were systematically searched from inception through November 2024 for relevant RCTs. Eligible studies were phase 2 or 3 RCTs that compared systemic or topical prophylactic interventions for the prevention of HFS. Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Risk of bias was assessed using the Cochrane Risk of Bias tool. A frequentist random-effects network meta-analysis was conducted. The primary income was incidence of grade 2 or higher HFS. The secondary outcome was the incidence of any-grade HFS. Odds ratios (ORs) with 95% CIs were estimated. Ranking was assessed using P-scores and surface under the cumulative ranking (SUCRA) values. Nineteen RCTs were included, of which 17 trials comprising 2192 patients (median [range] age, 57 [56-61] years) were analyzed for the primary outcome. Compared with placebo, topical silymarin (OR, 0.08; 95% CI, 0.01-0.71), diclofenac (OR, 0.23; 95% CI, 0.08-0.62), 400-mg pyridoxine (OR, 0.28; 95% CI, 0.09-0.88), and celecoxib (OR, 0.41; 95% CI, 0.18-0.95) significantly reduced grade 2 or higher HFS. Diclofenac (OR, 0.30; 95% CI, 0.13-0.69) and celecoxib (OR, 0.46; 95% CI, 0.22-0.94) also reduced overall HFS incidence. In contrast, silymarin and 400-mg pyridoxine did not show benefit for overall HFS, while mapisal increased HFS risk (OR, 3.04; 95% CI, 1.07-8.64). Ranking analyses showed the highest SUCRA value 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. Diclofenac emerged as the agent with the best overall supporting evidence, informed by both effect estimates and study quality.31:Te8e, Importance Hand-foot syndrome (HFS) is a common dose-limiting toxic effect of several chemotherapy agents, particularly capecitabine. Despite its substantial impact on the patient’s quality of life and potential to compromise therapeutic efficacy, effective preventive strategies remain limited. Objective To evaluate and compare the efficacy of pharmacologic interventions for the prevention of chemotherapy-induced HFS through a network meta-analysis of published results of randomized clinical trials (RCTs). Data Sources PubMed, Embase, and Cochrane CENTRAL were systematically searched from inception through November 2024 for relevant RCTs. Study Selection Eligible studies were phase 2 or 3 RCTs that compared systemic or topical prophylactic interventions for the prevention of HFS. Data Extraction and Synthesis Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Risk of bias was assessed using the Cochrane Risk of Bias tool. A frequentist random-effects network meta-analysis was conducted. Main Outcomes and Measures The primary income was incidence of grade 2 or higher HFS. The secondary outcome was the incidence of any-grade HFS. Odds ratios (ORs) with 95% CIs were estimated. Ranking was assessed using P-scores and surface under the cumulative ranking (SUCRA) values. Results Nineteen RCTs were included, of which 17 trials comprising 2192 patients (median [range] age, 57 [56-61] years) were analyzed for the primary outcome. Compared with placebo, topical silymarin (OR, 0.08; 95% CI, 0.01-0.71), diclofenac (OR, 0.23; 95% CI, 0.08-0.62), 400-mg pyridoxine (OR, 0.28; 95% CI, 0.09-0.88), and celecoxib (OR, 0.41; 95% CI, 0.18-0.95) significantly reduced grade 2 or higher HFS. Diclofenac (OR, 0.30; 95% CI, 0.13-0.69) and celecoxib (OR, 0.46; 95% CI, 0.22-0.94) also reduced overall HFS incidence. In contrast, silymarin and 400-mg pyridoxine did not show benefit for overall HFS, while mapisal increased HFS risk (OR, 3.04; 95% CI, 1.07-8.64). Ranking analyses showed the highest SUCRA value for silymarin (0.91) and diclofenac (0.76). Conclusions and Relevance 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. Diclofenac emerged as the agent with the best overall supporting evidence, informed by both effect estimates and study quality. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Hand-Foot Syndrome: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Hand-Foot Syndrome (condition). Clinician-written summaries and actionable practice insights. 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The benefit held after multivariable adjustment (adjusted HR 0.407; 95% CI 0.206–0.803; P=0.0096). Grade ≥3 HFS was also lower (3.8% vs. 15.6%; P=0.045). No steroid-related adverse events were observed.","limitations":"- Retrospective, non-randomized design with physician-determined allocation introduces confounding by indication that cannot be fully excluded.\n- No a priori sample size calculation; findings are exploratory and underpowered.\n- Dose reductions, treatment delays, and relative dose intensity were not systematically evaluated, leaving clinical impact on treatment delivery unclear.","practice_takeaway":"Applying a mid-strength topical steroid (e.g., hydrocortisone butyrate 0.1%) to palms and soles from day 1 of capecitabine may cut the risk of grade ≥2 HFS roughly in half, with no observed safety signals. Until prospective RCT data are available (e.g., J-DIRECT trial), this low-cost strategy is a reasonable option to discuss with patients starting CapeOX."}},{"doi":"10.1001/jamadermatol.2026.0042","pmid":"41779386","title":"Preventing Hand-Foot Syndrome in Patients With Cancer","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-03-04T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12961603/","source_score":33,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-19","doi":"10.1001/jamadermatol.2026.0042","days":"30","issn":"2168-6068","rank":"8","field":"Clinical Medicine","score":"33","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1001/jamadermatol.2026.0042","title":"Preventing Hand-Foot Syndrome in Patients With Cancer: A Systematic Review and Network Meta-Analysis.","journal":"JAMA dermatology","methods":"","results":"Nineteen RCTs were included, of which 17 trials comprising 2192 patients (median [range] age, 57 [56-61] years) were analyzed for the primary outcome. Compared with placebo, topical silymarin (OR, 0.08; 95% CI, 0.01-0.71), diclofenac (OR, 0.23; 95% CI, 0.08-0.62), 400-mg pyridoxine (OR, 0.28; 95% CI, 0.09-0.88), and celecoxib (OR, 0.41; 95% CI, 0.18-0.95) significantly reduced grade 2 or higher HFS. Diclofenac (OR, 0.30; 95% CI, 0.13-0.69) and celecoxib (OR, 0.46; 95% CI, 0.22-0.94) also reduced overall HFS incidence. In contrast, silymarin and 400-mg pyridoxine did not show benefit for overall HFS, while mapisal increased HFS risk (OR, 3.04; 95% CI, 1.07-8.64). Ranking analyses showed the highest SUCRA value for silymarin (0.91) and diclofenac (0.76).","abstract":"$30","keywords":[],"pubmed_id":"41779386","conclusions":"","publication_date":"2026-03-04T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2026.0042","URL":"https://doi.org/10.1001/jamadermatol.2026.0042","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2845560/jamadermatology_baskarane_2026_oi_260002_1775760776.72378.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"386","type":"journal-article","issue":"4","score":1,"title":["Preventing Hand-Foot Syndrome in Patients With Cancer"],"author":[{"given":"Hemavathi","family":"Baskarane","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Shubham","family":"Sahni","sequence":"additional","affiliation":[{"name":"Department of Medical 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India"}]}],"issued":{"date-parts":[[2026,4,1]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"162","created":{"date-time":"2026-03-04T16:30:40Z","timestamp":1772641840000,"date-parts":[[2026,3,4]]},"indexed":{"date-time":"2026-04-15T15:51:16Z","timestamp":1776268276641,"date-parts":[[2026,4,15]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamadermatology/fullarticle/2845560"}},"subtitle":["A Systematic Review and Network Meta-Analysis"],"deposited":{"date-time":"2026-04-15T15:00:25Z","timestamp":1776265225000,"date-parts":[[2026,4,15]]},"issn-type":[{"type":"print","value":"2168-6068"}],"published":{"date-parts":[[2026,4,1]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1002/jgm.3289","key":"doi260002r1","year":"2021","issue":"1","author":"Naushad","volume":"23","first-page":null,"unstructured":null,"article-title":"Pharmacogenetic profiling of dihydropyrimidine 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Diclofenac had the broadest evidence, reducing both grade ≥2 and any-grade HFS (OR 0.30). Notably, mapisal *increased* HFS risk (OR 3.04). Silymarin ranked highest by SUCRA (0.91) but rests on limited trial data.","limitations":"- Silymarin's strong effect estimate comes from a single small trial and needs confirmation in a larger RCT.\n- Network meta-analysis relies on indirect comparisons; heterogeneity across trials in HFS grading and chemotherapy regimens may affect estimates.\n- Median age range is narrow (56–61 years), limiting generalizability to older or pediatric populations.","practice_takeaway":"For patients starting capecitabine, topical diclofenac has the strongest overall evidence for preventing clinically significant (grade ≥2) HFS and should be considered as a prophylactic option. 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