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:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Topical Anti-Inflammatory: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Topical Anti-Inflammatory (modality). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/modality/Topical%20Anti-Inflammatory\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Modalities\",\"item\":\"https://www.reachrx.ai/hub/tag/modality\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Topical Anti-Inflammatory\",\"item\":\"https://www.reachrx.ai/hub/tag/modality/Topical%20Anti-Inflammatory\"}]}}"}}]],["$","$L2f",null,{"title":"Topical Anti-Inflammatory: Research & Clinical Takeaways","description":"Review evidence by treatment modality: Topical Anti-Inflammatory — concise summaries and practical next steps.","papers":[{"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 Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Chitrakshi","family":"Nagpal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Mohit Kumar","family":"Divakar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Neha","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Sudhir","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Sameer","family":"Bakhshi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Hari Krishna Raju","family":"Sagiraju","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Pranav Pratap","family":"Singh","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Rishika","family":"Agarwal","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Vishakha","family":"Hooda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Payal","family":"Vasudeva","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India"}]},{"given":"Atul","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, 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 dehydrogenase (DPYD) variants in the Indian population.","journal-title":"J Gene Med","doi-asserted-by":"publisher"},{"DOI":null,"key":"doi260002r2","year":"2006","issue":"5","author":"Janusch","volume":"16","first-page":"494","unstructured":null,"article-title":"The hand-foot syndrome–a frequent secondary manifestation in antineoplastic chemotherapy.","journal-title":"Eur J Dermatol","doi-asserted-by":null},{"DOI":"10.3332/ecancer.2022.1390","key":"doi260002r3","year":"2022","issue":null,"author":"de Queiroz","volume":"16","first-page":"1390","unstructured":null,"article-title":"Hand-foot syndrome caused by capecitabine: incidence, risk factors and the role of dermatological evaluation.","journal-title":"Ecancermedicalscience","doi-asserted-by":"publisher"},{"DOI":"10.4081/oncol.2020.442","key":"doi260002r4","year":"2020","issue":"1","author":"Kwakman","volume":"14","first-page":"442","unstructured":null,"article-title":"Management of cytotoxic chemotherapy-induced hand-foot syndrome.","journal-title":"Oncol Rev","doi-asserted-by":"publisher"},{"DOI":"10.7759/cureus.969","key":"doi260002r5","year":"2017","issue":"1","author":"Cohen","volume":"9","first-page":null,"unstructured":null,"article-title":"Capecitabine-associated loss of fingerprints: report of capecitabine-induced adermatoglyphia in two women with breast cancer and review of acquired dermatoglyphic absence in oncology patients treated with capecitabine.","journal-title":"Cureus","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa1612645","key":"doi260002r6","year":"2017","issue":"22","author":"Masuda","volume":"376","first-page":"2147","unstructured":null,"article-title":"Adjuvant capecitabine for breast cancer after preoperative chemotherapy.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(11)61873-4","key":"doi260002r7","year":"2012","issue":"9813","author":"Bang","volume":"379","first-page":"315","unstructured":null,"article-title":"Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.","journal-title":"Lancet","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa1713709","key":"doi260002r8","year":"2018","issue":"13","author":"Grothey","volume":"378","first-page":"1177","unstructured":null,"article-title":"Duration of adjuvant chemotherapy for stage III colon cancer.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa064320","key":"doi260002r9","year":"2006","issue":"26","author":"Geyer","volume":"355","first-page":"2733","unstructured":null,"article-title":"Lapatinib plus capecitabine for HER2-positive advanced breast cancer.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1634/theoncologist.2011-0033","key":"doi260002r10","year":"2011","issue":"10","author":"Sibaud","volume":"16","first-page":"1469","unstructured":null,"article-title":"HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome.","journal-title":"Oncologist","doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdg500","key":"doi260002r11","year":"2003","issue":"12","author":"Scheithauer","volume":"14","first-page":"1735","unstructured":null,"article-title":"Oral capecitabine as an alternative to IV 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial.","journal-title":"Ann Oncol","doi-asserted-by":"publisher"},{"DOI":"10.3393/jksc.2010.26.4.287","key":"doi260002r12","year":"2010","issue":"4","author":"Yun","volume":"26","first-page":"287","unstructured":null,"article-title":"Oncologic outcome after cessation or dose reduction of capecitabine in patients with colon cancer.","journal-title":"J Korean Soc Coloproctol","doi-asserted-by":"publisher"},{"DOI":"10.1200/OA-24-00068","key":"doi260002r13","year":"2025","issue":"1","author":"Khan","volume":"2","first-page":null,"unstructured":null,"article-title":"Randomized trial of fixed-dose capecitabine compared with standard-dose capecitabine in metastatic breast cancer: X-7/7 trial.","journal-title":"JCO Oncol Adv","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12885-022-10026-3","key":"doi260002r14","year":"2022","issue":"1","author":"Jiang","volume":"22","first-page":"950","unstructured":null,"article-title":"Tolerance to oral anticancer agent treatment in older adults with cancer: a secondary analysis of data from electronic health records and a pilot study of patient-reported outcomes.","journal-title":"BMC Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1021/acs.chemrestox.6b00215","key":"doi260002r16","year":"2016","issue":"10","author":"Lou","volume":"29","first-page":"1591","unstructured":null,"article-title":"Possible pathways of capecitabine-induced hand-foot syndrome.","journal-title":"Chem Res Toxicol","doi-asserted-by":"publisher"},{"DOI":"10.1139/cjpp-2022-0439","key":"doi260002r17","year":"2023","issue":"7","author":"Mashaly","volume":"101","first-page":"340","unstructured":null,"article-title":"Thymidine phosphorylase as a molecular target for quercetin-incorporated collagen matrix in the prevention of hand-foot syndrome induced by capecitabine in rats.","journal-title":"Can J Physiol Pharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1038/s41416-022-02039-3","key":"doi260002r18","year":"2023","issue":"2","author":"Yang","volume":"128","first-page":"219","unstructured":null,"article-title":"Capecitabine induces hand-foot syndrome through elevated thymidine phosphorylase-mediated locoregional toxicity and GSDME-driven pyroptosis that can be relieved by tipiracil.","journal-title":"Br J Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1007/s13577-012-0057-0","key":"doi260002r19","year":"2013","issue":"1","author":"Yokomichi","volume":"26","first-page":"8","unstructured":null,"article-title":"Pathogenesis of hand-foot syndrome induced by PEG-modified liposomal doxorubicin.","journal-title":"Hum Cell","doi-asserted-by":"publisher"},{"DOI":null,"key":"doi260002r20","year":"2009","issue":"6","author":"Martschick","volume":"29","first-page":"2307","unstructured":null,"article-title":"The pathogenetic mechanism of anthracycline-induced palmar-plantar erythrodysesthesia.","journal-title":"Anticancer Res","doi-asserted-by":null},{"DOI":"10.3727/096504018X15291727589740","key":"doi260002r21","year":"2019","issue":"5","author":"Nonomiya","volume":"27","first-page":"551","unstructured":null,"article-title":"Regorafenib-induced hand-foot skin reaction is more severe on the feet than on the hands.","journal-title":"Oncol Res","doi-asserted-by":"publisher"},{"DOI":"10.1080/02841860701765675","key":"doi260002r22","year":"2008","issue":"2","author":"Chu","volume":"47","first-page":"176","unstructured":null,"article-title":"Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis.","journal-title":"Acta Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdn389","key":"doi260002r23","year":"2008","issue":"11","author":"Lacouture","volume":"19","first-page":"1955","unstructured":null,"article-title":"Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib.","journal-title":"Ann Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1634/theoncologist.2008-0131","key":"doi260002r24","year":"2008","issue":"9","author":"Lacouture","volume":"13","first-page":"1001","unstructured":null,"article-title":"Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib.","journal-title":"Oncologist","doi-asserted-by":"publisher"},{"DOI":"10.1111/j.1365-2125.2008.03159.x","key":"doi260002r25","year":"2008","issue":"1","author":"Milano","volume":"66","first-page":"88","unstructured":null,"article-title":"Candidate mechanisms for capecitabine-related hand-foot syndrome.","journal-title":"Br J Clin Pharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2014.03.019","key":"doi260002r26","year":"2014","issue":"4","author":"Miller","volume":"71","first-page":"787","unstructured":null,"article-title":"Chemotherapy-induced hand-foot syndrome and nail changes: a review of clinical presentation, etiology, pathogenesis, and management.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1021/acs.chemrestox.1c00317","key":"doi260002r27","year":"2022","issue":"3","author":"He","volume":"35","first-page":"422","unstructured":null,"article-title":"P38 MAPK, NF-?B, and JAK-STAT3 signaling pathways involved in capecitabine-induced hand-foot syndrome via interleukin 6 or interleukin 8 abnormal expression.","journal-title":"Chem Res Toxicol","doi-asserted-by":"publisher"},{"DOI":"10.1007/s00520-018-4054-z","key":"doi260002r28","year":"2018","issue":"7","author":"Bun","volume":"26","first-page":"2161","unstructured":null,"article-title":"Symptom management: the utility of regional cooling for hand-foot syndrome induced by pegylated liposomal doxorubicin in ovarian cancer.","journal-title":"Support Care Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ygyno.2007.10.021","key":"doi260002r29","year":"2008","issue":"2","author":"Mangili","volume":"108","first-page":"332","unstructured":null,"article-title":"Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling.","journal-title":"Gynecol Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1002/cncr.23333","key":"doi260002r30","year":"2008","issue":"7","author":"Scotté","volume":"112","first-page":"1625","unstructured":null,"article-title":"Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot.","journal-title":"Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdr400","key":"doi260002r31","year":"2012","issue":"5","author":"Zhang","volume":"23","first-page":"1348","unstructured":null,"article-title":"Celecoxib can prevent capecitabine-related hand-foot syndrome in stage II and III colorectal cancer patients: result of a single-center, prospective randomized phase III trial.","journal-title":"Ann Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.23.01730","key":"doi260002r32","year":"2024","issue":"15","author":"Santhosh","volume":"42","first-page":"1821","unstructured":null,"article-title":"Topical diclofenac for prevention of capecitabine-associated hand-foot syndrome: a double-blind randomized controlled trial.","journal-title":"J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1136/spcare-2022-004011","key":"doi260002r33","year":"2024","issue":"e2","author":"Ramasubbu","volume":"14","first-page":"e1575","unstructured":null,"article-title":"Chemotherapy-induced hand foot syndrome: comparative efficacy and safety of pharmacological prophylaxis – systematic review and Bayesian network meta-analysis.","journal-title":"BMJ Support Palliat Care","doi-asserted-by":"publisher"},{"DOI":"10.1001/jamaoncol.2017.1269","key":"doi260002r34","year":"2017","issue":"11","author":"Yap","volume":"3","first-page":"1538","unstructured":null,"article-title":"Predictors of hand-foot syndrome and pyridoxine for prevention of capecitabine-induced hand-foot syndrome: a randomized clinical trial.","journal-title":"JAMA Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.2014.60.4587","key":"doi260002r35","year":"2015","issue":"22","author":"Hofheinz","volume":"33","first-page":"2444","unstructured":null,"article-title":"Mapisal versus urea cream as prophylaxis for capecitabine-associated hand-foot syndrome: a randomized phase III trial of the AIO quality of life working group.","journal-title":"J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.2010.31.1431","key":"doi260002r36","year":"2010","issue":"35","author":"Wolf","volume":"28","first-page":"5182","unstructured":null,"article-title":"Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study.","journal-title":"J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1002/cncr.25262","key":"doi260002r37","year":"2010","issue":"20","author":"von Gruenigen","volume":"116","first-page":"4735","unstructured":null,"article-title":"A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients.","journal-title":"Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1111/j.1743-7563.2010.01311.x","key":"doi260002r38","year":"2010","issue":"3","author":"Chalermchai","volume":"6","first-page":"155","unstructured":null,"article-title":"Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia.","journal-title":"Asia Pac J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.2010.29.1807","key":"doi260002r39","year":"2010","issue":"24","author":"Kang","volume":"28","first-page":"3824","unstructured":null,"article-title":"Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study.","journal-title":"J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.31557/APJCP.2024.25.6.2203","key":"doi260002r40","year":"2024","issue":"6","author":"Wanichtanom","volume":"25","first-page":"2203","unstructured":null,"article-title":"A randomized single-blinded phase II trial comparing efficacy and quality of life of topical aloe vera gel plus urea cream versus urea cream alone for prevention of hand foot syndrome in cancer patients receiving capecitabine.","journal-title":"Asian Pac J Cancer Prev","doi-asserted-by":"publisher"},{"DOI":"10.1002/ptr.5857","key":"doi260002r41","year":"2017","issue":"9","author":"Elyasi","volume":"31","first-page":"1323","unstructured":null,"article-title":"Topical silymarin administration for prevention of capecitabine-induced hand-foot syndrome: a randomized, double-blinded, placebo-controlled clinical trial.","journal-title":"Phytother Res","doi-asserted-by":"publisher"},{"DOI":"10.21037/apm-21-61","key":"doi260002r42","year":"2021","issue":"3","author":"Lu","volume":"10","first-page":"3009","unstructured":null,"article-title":"The effectiveness of EVOSKIN Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.","journal-title":"Ann Palliat Med","doi-asserted-by":"publisher"},{"DOI":"10.1007/s12664-020-01039-6","key":"doi260002r43","year":"2020","issue":"2","author":"Watanabe","volume":"39","first-page":"204","unstructured":null,"article-title":"The effect of TJ-28 (eppikajutsuto) on the prevention of hand-foot syndrome using Capecitabine for colorectal cancer: the Yokohama Clinical Oncology Group Study (YCOG1102).","journal-title":"Indian J Gastroenterol","doi-asserted-by":"publisher"},{"DOI":"10.1007/s12282-018-0879-z","key":"doi260002r44","year":"2018","issue":"6","author":"Toyama","volume":"25","first-page":"729","unstructured":null,"article-title":"A randomized phase II study evaluating pyridoxine for the prevention of hand-foot syndrome associated with capecitabine therapy for advanced or metastatic breast cancer.","journal-title":"Breast Cancer","doi-asserted-by":"publisher"},{"DOI":"10.12788/jcso.0017","key":"doi260002r45","year":"2014","issue":"2","author":"Braik","volume":"12","first-page":"65","unstructured":null,"article-title":"Randomized trial of vitamin B6 for preventing hand-foot syndrome from capecitabine chemotherapy.","journal-title":"J Community Support Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1038/bjc.2012.318","key":"doi260002r46","year":"2012","issue":"4","author":"Corrie","volume":"107","first-page":"585","unstructured":null,"article-title":"A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.","journal-title":"Br J Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1177/15347354221140402","key":"doi260002r47","year":"2022","issue":null,"author":"Xiaozhe","volume":"21","first-page":null,"unstructured":null,"article-title":"Pyridoxine is effective for preventing hand-foot syndrome induced by pegylated liposomal doxorubicin for multiple myeloma: the results of a randomized study.","journal-title":"Integr Cancer Ther","doi-asserted-by":"publisher"},{"DOI":"10.5152/FNJN.2020.19097","key":"doi260002r48","year":"2020","issue":"3","author":"Kayikci","volume":"28","first-page":"299","unstructured":null,"article-title":"Henna Application in the prevention of capecitabine-induced hand-foot syndrome in breast and colorectal cancer patients.","journal-title":"Florence Nightingale J Nurs","doi-asserted-by":"publisher"},{"DOI":"10.1177/1534735420928466","key":"doi260002r49","year":"2020","issue":null,"author":"Yu","volume":"19","first-page":null,"unstructured":null,"article-title":"Effect of Chinese herbal compound LC09 on patients with capecitabine-associated hand-foot syndrome: a randomized, double-blind, and parallel-controlled trial.","journal-title":"Integr Cancer Ther","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.clbc.2022.01.009","key":"doi260002r50","year":"2022","issue":"5","author":"Xie","volume":"22","first-page":"e685","unstructured":null,"article-title":"Effect of a novel soaking solution used in patients with hand-foot syndrome as a result of capecitabine treatment: a randomized and self-controlled trial.","journal-title":"Clin Breast Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1002/ptr.5704","key":"doi260002r51","year":"2016","issue":"11","author":"Elyasi","volume":"30","first-page":"1879","unstructured":null,"article-title":"Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: a randomized, double-blinded, placebo-controlled clinical trial.","journal-title":"Phytother Res","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.phymed.2009.02.002","key":"doi260002r52","year":"2009","issue":"5","author":"El-Kamary","volume":"16","first-page":"391","unstructured":null,"article-title":"A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.","journal-title":"Phytomedicine","doi-asserted-by":"publisher"},{"DOI":"10.1016/S0923-7534(20)33033-7","key":"doi260002r53","year":"2012","issue":null,"author":"Altaei","volume":"23","first-page":"ix163","unstructured":null,"article-title":"Treatment of chemotherapy-induced oral mucositis by silymarin.","journal-title":"Ann Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1002/ptr.6231","key":"doi260002r54","year":"2019","issue":"2","author":"Karbasforooshan","volume":"33","first-page":"379","unstructured":null,"article-title":"Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: a randomized, double-blind, placebo-controlled clinical trial.","journal-title":"Phytother Res","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12885-025-13684-1","key":"doi260002r55","year":"2025","issue":"1","author":"Wongkraisri","volume":"25","first-page":"275","unstructured":null,"article-title":"Randomized controlled trial on the efficacy of topical urea-based cream in preventing capecitabine-associated hand-foot syndrome.","journal-title":"BMC Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1007/s00520-022-07175-3","key":"doi260002r56","year":"2022","issue":"11","author":"Pandy","volume":"30","first-page":"8655","unstructured":null,"article-title":"Prophylactic strategies for hand-foot syndrome/skin reaction associated with systemic cancer treatment: a meta-analysis of randomized controlled trials.","journal-title":"Support Care Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12891-025-08465-7","key":"doi260002r57","year":"2025","issue":"1","author":"Chen","volume":"26","first-page":"230","unstructured":null,"article-title":"Efficacy and safety of different topical diclofenac formulations for the treatment of knee osteoarthritis: a meta-analysis of short-term and long-term treatment comparisons.","journal-title":"BMC Musculoskelet Disord","doi-asserted-by":"publisher"},{"DOI":"10.1007/s40744-020-00196-6","key":"doi260002r58","year":"2020","issue":"2","author":"Bariguian Revel","volume":"7","first-page":"217","unstructured":null,"article-title":"Topical diclofenac, an efficacious treatment for osteoarthritis: a narrative review.","journal-title":"Rheumatol Ther","doi-asserted-by":"publisher"},{"DOI":"10.2147/CIA.S35416","key":"doi260002r59","year":"2012","issue":null,"author":"Peniston","volume":"7","first-page":"517","unstructured":null,"article-title":"Long-term tolerability of topical diclofenac sodium 1% gel for osteoarthritis in seniors and patients with comorbidities.","journal-title":"Clin Interv Aging","doi-asserted-by":"publisher"},{"DOI":"10.1007/s40122-025-00723-9","key":"doi260002r60","year":"2025","issue":"3","author":"Sicignano","volume":"14","first-page":"1007","unstructured":null,"article-title":"Evaluating the real-world use of topical diclofenac sodium gel 1% using US longitudinal electronic health records database: a study supporting OTC switch.","journal-title":"Pain Ther","doi-asserted-by":"publisher"},{"DOI":"10.1002/cpt.911","key":"doi260002r61","year":"2018","issue":"2","author":"Amstutz","volume":"103","first-page":"210","unstructured":null,"article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update.","journal-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher"},{"DOI":"10.1038/s41416-024-02754-z","key":"doi260002r62","year":"2024","issue":"3","author":"Chan","volume":"131","first-page":"498","unstructured":null,"article-title":"DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.","journal-title":"Br J Cancer","doi-asserted-by":"publisher"},{"DOI":null,"key":"doi260002r15","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE), version 6. Accessed June 17, 2025. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1200/JCO.2016.34.15_suppl.e13018","key":"doi260002r63","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Peoples? AM, Ahmed? G, Galiauskas? R, . Polymorphisms in TPMT and TYMS may predict severe toxicity in DPYD wild-type patients receiving fluoropyrimidine (FP) chemotherapy for colorectal cancer. J Clin Oncol. 2016;34:e13018. doi:10.1200/JCO.2016.34.15_suppl.e13018","article-title":null,"journal-title":null,"doi-asserted-by":"crossref"}],"short-title":[],"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Dermatology"],"published-print":{"date-parts":[[2026,4,1]]},"reference-count":63,"published-online":null,"references-count":63,"short-container-title":["JAMA Dermatol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamadermatol.2026.0042","is_oa":true,"title":"Preventing Hand-Foot Syndrome in Patients With Cancer","updated":"2026-03-07T18:31:02+00:00","published_date":"2026-03-04","best_oa_location":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12961603/","pmh_id":"oai:pubmedcentral.nih.gov:12961603","url_for_pdf":null,"url_for_landing_page":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12961603/"}}},"created_at":"2026-05-07T17:34:02.008Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"condition","value":"Hand-Foot Syndrome","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"capecitabine","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"celecoxib","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"diclofenac","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"mapisal","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"pyridoxine","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"generic","value":"silymarin","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"modality","value":"Antioxidant","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"modality","value":"COX-2 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"modality","value":"Topical Anti-Inflammatory","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"modality","value":"Vitamin B6 Supplement","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"sample_size","value":"n=2192","value_numeric":2192},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"warning","value":"Full text is under PMC embargo until March 2027; summary is based solely on the abstract and results excerpt provided.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"warning","value":"Sex distribution across trials is not explicitly reported in the abstract; 'mixed' is assumed based on cancer population context.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"warning","value":"Silymarin's exceptionally low OR (0.08) should be interpreted cautiously given it derives from a single small trial—the authors themselves call for confirmatory RCT evidence.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0042","tag_type":"warning","value":"The impact_flag 'practice_changing' and 'safety_signal' are both tagged: practice_changing for diclofenac's evidence base, and safety_signal for mapisal's unexpected harm signal.","value_numeric":null}],"summaries":{"what_studied":"This network meta-analysis of 19 RCTs (17 contributing to the primary outcome; n=2,192 patients; median age 57 years) evaluated pharmacologic interventions—topical and systemic—for preventing chemotherapy-induced hand-foot syndrome (HFS), primarily from capecitabine.","key_result":"Compared with placebo, topical silymarin (OR 0.08), diclofenac (OR 0.23), high-dose pyridoxine 400 mg (OR 0.28), and celecoxib (OR 0.41) each significantly reduced grade ≥2 HFS. 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. Avoid mapisal, which was associated with *increased* HFS risk in this analysis."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Topical Anti-Inflammatory"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Topical Anti-Inflammatory"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Topical Anti-Inflammatory"}}}]]

Papers