{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:03:43Z","timestamp":1780013023002,"version":"3.53.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007338","name":"All-India Institute of Medical Sciences","doi-asserted-by":"publisher","award":["No.F.5-59\/IRG\/2010\/RS"],"award-info":[{"award-number":["No.F.5-59\/IRG\/2010\/RS"]}],"id":[{"id":"10.13039\/501100007338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute pain syndrome (APS) is a common side effect of paclitaxel therapy. To date, there is no standard of care to prevent APS in patients receiving paclitaxel. Through this study, we aim to assess whether oral duloxetine reduces the incidence of paclitaxel-induced APS (P-APS) as compared to placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a multi-centric, randomized (1:1), double-blind, placebo-controlled, parallel-group superiority trial. A total of 204 patients with breast cancer planned to receive paclitaxel will be randomly assigned to receive either oral duloxetine or a matched placebo for 7\u00a0days after paclitaxel infusions for 4 cycles. The primary objective of the study is to compare the proportion of patients who develop P-APS in two groups. Key secondary objectives are to compare the quality of life (using the FACT-B scale), the incidence of peripheral neuropathy, the safety profile, and adherence with duloxetine. Patient-reported outcomes for P-APS and neuropathy will be assessed at the end of each cycle using BPI-SF and EORTC-CIPN20 questionnaires, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The DOPA study is designed to evaluate whether oral duloxetine can reduce the occurrence of APS in patients receiving paclitaxel chemotherapy for breast cancer. Limited trials have assessed P-APS prevention using etoricoxib, dexamethasone, and pregabalin, but no pharmacological measure is effective. If the trial successfully meets its primary endpoint, oral duloxetine could become the new standard of care for preventing paclitaxel-induced APS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Clinical Trials Registry of India \u2013 CTRI\/2024\/10\/075636. Registered on 22 October 2024.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-026-09673-9","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T05:37:54Z","timestamp":1776490674000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Randomized, double-blind, placebo-controlled study of oral duloxetine in prevention of acute pain syndrome in breast cancer patients receiving paclitaxel (DOPA study)"],"prefix":"10.1186","volume":"27","author":[{"given":"Jahnavi","family":"Banotra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vrajesh Veenadhar","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Bakhshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achal Kumar","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhat","family":"Bhargava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharath","family":"Gangadhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Vasudeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriti","family":"Pallavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamesh","family":"Bhati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlok","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit Kumar","family":"Divakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemavathi","family":"Baskarane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-8408","authenticated-orcid":false,"given":"Atul","family":"Batra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"issue":"5","key":"9673_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2217\/pgs.10.32","volume":"11","author":"C Rodr\u00edguez-Antona","year":"2010","unstructured":"Rodr\u00edguez-Antona C. Pharmacogenomics of paclitaxel. Pharmacogenomics. 2010;11(5):621\u20133.","journal-title":"Pharmacogenomics"},{"issue":"1","key":"9673_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01657-2","volume":"29","author":"P Sati","year":"2024","unstructured":"Sati P, Sharma E, Dhyani P, Attri DC, Rana R, Kiyekbayeva L, et al. Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties. Eur J Med Res. 2024;29(1):90.","journal-title":"Eur J Med Res"},{"issue":"20","key":"9673_CR3","doi-asserted-by":"publisher","first-page":"5171","DOI":"10.1002\/cncr.27489","volume":"118","author":"BN Reeves","year":"2012","unstructured":"Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, et al. Further data supporting that the paclitaxel-associated acute pain syndrome is associated with the development of peripheral neuropathy: NCCTG trial N08C1. Cancer. 2012;118(20):5171\u20138.","journal-title":"Cancer"},{"issue":"11","key":"9673_CR4","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1200\/JCO.2010.33.0308","volume":"29","author":"CL Loprinzi","year":"2011","unstructured":"Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, et al. Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol. 2011;29(11):1472\u20138.","journal-title":"J Clin Oncol"},{"issue":"8","key":"9673_CR5","first-page":"2261","volume":"22","author":"F Mols","year":"2014","unstructured":"Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L. Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer. 2014;22(8):2261\u20139.","journal-title":"Support Care Cancer"},{"issue":"6","key":"9673_CR6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1097\/PPO.0b013e31815a999b","volume":"13","author":"CL Loprinzi","year":"2007","unstructured":"Loprinzi CL, Maddocks-Christianson K, Wolf SL, Rao RD, Dyck PJB, Mantyh P, et al. The paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J. 2007;13(6):399\u2013403.","journal-title":"Cancer J"},{"key":"9673_CR7","unstructured":"Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties | Eur J Med Res| Full Text. Available from: https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-024-01657-2. Cited 2025 Aug 22."},{"issue":"1\u20132","key":"9673_CR8","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.pain.2004.01.021","volume":"109","author":"PM Dougherty","year":"2004","unstructured":"Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004;109(1\u20132):132\u201342.","journal-title":"Pain"},{"issue":"3","key":"9673_CR9","first-page":"315","volume":"17","author":"T Yoshida","year":"2009","unstructured":"Yoshida T, Sawa T, Ishiguro T, Horiba A, Minatoguchi S, Fujiwara H. The efficacy of prophylactic Shakuyaku-Kanzo-to for myalgia and arthralgia following carboplatin and paclitaxel combination chemotherapy for non-small cell lung cancer. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2009;17(3):315\u201320.","journal-title":"Support Care Cancer Off J Multinatl Assoc Support Care Cancer"},{"issue":"1","key":"9673_CR10","first-page":"221","volume":"28","author":"Y Saito","year":"2020","unstructured":"Saito Y, Kobayashi M, Yamada T, Sakakibara-Konishi J, Shinagawa N, Kinoshita I, et al. Efficacy of additional dexamethasone administration for the attenuation of paclitaxel-associated acute pain syndrome. Support Care Cancer. 2020;28(1):221\u20137.","journal-title":"Support Care Cancer"},{"key":"9673_CR11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.ejca.2022.05.019","volume":"171","author":"J Zhang","year":"2022","unstructured":"Zhang J, Gao HF, Yang C, Zhu T, Ji F, Yang M, et al. Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: a phase II randomised trial. Eur J Cancer. 2022;171:150\u201360.","journal-title":"Eur J Cancer"},{"issue":"2","key":"9673_CR12","first-page":"547","volume":"24","author":"SS Shinde","year":"2016","unstructured":"Shinde SS, Seisler D, Soori G, Atherton PJ, Pachman DR, Lafky J, et al. Can pregabalin prevent paclitaxel-associated neuropathy?\u2013an ACCRU pilot trial. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2016;24(2):547\u201353.","journal-title":"Support Care Cancer Off J Multinatl Assoc Support Care Cancer"},{"issue":"9","key":"9673_CR13","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1200\/JCO.2004.99.298","volume":"22","author":"VH Nguyen","year":"2004","unstructured":"Nguyen VH, Lawrence HJ. Use of gabapentin in the prevention of taxane-induced arthralgias and myalgias. J Clin Oncol. 2004;22(9):1767\u20139.","journal-title":"J Clin Oncol"},{"issue":"4","key":"9673_CR14","first-page":"274","volume":"1","author":"SD Jacobson","year":"2003","unstructured":"Jacobson SD, Loprinzi CL, Sloan JA, Wilke JL, Novotny PJ, Okuno SH, et al. Glutamine does not prevent paclitaxel-associated myalgias and arthralgias. J Support Oncol. 2003;1(4):274\u20138.","journal-title":"J Support Oncol"},{"key":"9673_CR15","first-page":"99","volume":"2","author":"BA Scholz","year":"2009","unstructured":"Scholz BA, Hammonds CL, Boomershine CS. Duloxetine for the management of fibromyalgia syndrome. J Pain Res. 2009;2:99\u2013108.","journal-title":"J Pain Res"},{"issue":"12","key":"9673_CR16","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1185\/03007995.2011.633502","volume":"27","author":"EP Frakes","year":"2011","unstructured":"Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011;27(12):2361\u201372.","journal-title":"Curr Med Res Opin"},{"key":"9673_CR17","first-page":"343","volume":"5","author":"MJ Ormseth","year":"2011","unstructured":"Ormseth MJ, Scholz BA, Boomershine CS. Duloxetine in the management of diabetic peripheral neuropathic pain. Patient Prefer Adherence. 2011;5:343\u201356.","journal-title":"Patient Prefer Adherence"},{"key":"9673_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00365","volume":"10","author":"J Meng","year":"2019","unstructured":"Meng J, Zhang Q, Yang C, Xiao L, Xue Z, Zhu J. Duloxetine, a balanced serotonin-norepinephrine reuptake inhibitor, improves painful chemotherapy-induced peripheral neuropathy by inhibiting activation of p38 MAPK and NF-\u03baB. Front Pharmacol. 2019;10:365.","journal-title":"Front Pharmacol"},{"key":"9673_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.554899","volume":"11","author":"D Rodrigues-Amorim","year":"2020","unstructured":"Rodrigues-Amorim D, Olivares JM, Spuch C, Rivera-Baltan\u00e1s T. A systematic review of efficacy, safety, and tolerability of duloxetine. Front Psychiatry. 2020;11:554899.","journal-title":"Front Psychiatry"},{"issue":"10","key":"9673_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/toxics9100229","volume":"9","author":"I Klein","year":"2021","unstructured":"Klein I, Lehmann HC. Pathomechanisms of paclitaxel-induced peripheral neuropathy. Toxics. 2021;9(10):229.","journal-title":"Toxics"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-026-09673-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09673-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09673-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T23:48:48Z","timestamp":1780012128000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13063-026-09673-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9673"],"URL":"https:\/\/doi.org\/10.1186\/s13063-026-09673-9","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]},"assertion":[{"value":"3 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol has been reviewed and approved by the Institutional Ethics Committee of the All India Institute of Medical Sciences, New Delhi; Ref. No.: AIIMSA1239\/05.04.2024.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"400"}}