{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:58:06Z","timestamp":1793177886629,"version":"4.5.0"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Frantz Viral Therapeutics"},{"name":"Frantz Viral Therapeutics, LLC"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Artesunate suppositories are a safe treatment option for anal HSIL.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0295647","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T18:38:32Z","timestamp":1702665512000},"page":"e0295647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-6968","authenticated-orcid":true,"given":"Sandy Hwang","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Plesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evie H.","family":"Carchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Cowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Staudt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyleigh Ann","family":"Twaroski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6671-0115","authenticated-orcid":true,"given":"Ulrike K.","family":"Buchwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia L.","family":"Trimble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"issue":"S10","key":"pone.0295647.ref001","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/cncr.23744","article-title":"Understanding the burden of human papillomavirus-associated anal cancers in the US","volume":"113","author":"DA Joseph","year":"2008","journal-title":"Cancer"},{"issue":"24","key":"pone.0295647.ref002","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1056\/NEJMoa2201048","article-title":"Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer","volume":"386","author":"JM Palefsky","year":"2022","journal-title":"N Engl J Med"},{"issue":"7","key":"pone.0295647.ref003","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1002\/cncr.32581","article-title":"Electrocautery ablation of anal high-grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes","volume":"126","author":"MM Gaisa","year":"2020","journal-title":"Cancer"},{"issue":"2","key":"pone.0295647.ref004","first-page":"e0245870","article-title":"Risk factors for >\/ = high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments.","volume":"16","author":"C Hidalgo-Tenorio","year":"2021","journal-title":"PubMed Central PMCID"},{"key":"pone.0295647.ref005","doi-asserted-by":"crossref","DOI":"10.30875\/6c551ba0-en","author":"Organization WH","year":"2021","journal-title":"World malaria report 2021: An in-depth update on global and regional malaria data and trends"},{"key":"pone.0295647.ref006","doi-asserted-by":"crossref","first-page":"112044","DOI":"10.1016\/j.ejmech.2020.112044","article-title":"Artemisinin-derived hybrids and their anticancer activity","volume":"188","author":"F Gao","year":"2020","journal-title":"Eur J Med Chem"},{"key":"pone.0295647.ref007","first-page":"1","article-title":"Antimalarial and anticancer properties of artesunate and other artemisinins: current development","author":"P. Khanal","year":"2021","journal-title":"Monatshefte fur chemie"},{"issue":"4","key":"pone.0295647.ref008","doi-asserted-by":"crossref","first-page":"647","DOI":"10.2217\/fon.13.228","article-title":"Use of artemisinin and its derivatives to treat HPV-infected\/transformed cells and cervical cancer: a review","volume":"10","author":"SK Goodrich","year":"2014","journal-title":"Future Oncol"},{"issue":"23","key":"pone.0295647.ref009","doi-asserted-by":"crossref","first-page":"10854","DOI":"10.1158\/0008-5472.CAN-05-1216","article-title":"Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo","volume":"65","author":"GL Disbrow","year":"2005","journal-title":"Cancer Res"},{"issue":"12","key":"pone.0295647.ref010","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1021\/jm030571c","article-title":"A medicinal chemistry perspective on artemisinin and related endoperoxides","volume":"47","author":"PM O\u2019Neill","year":"2004","journal-title":"J Med Chem"},{"issue":"21","key":"pone.0295647.ref011","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1001\/jama.297.21.2381","article-title":"Rectal administration of artemisinin derivatives for the treatment of malaria","volume":"297","author":"HA Karunajeewa","year":"2007","journal-title":"Jama"},{"issue":"1","key":"pone.0295647.ref012","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ygyno.2019.12.035","article-title":"A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2\/3 (CIN2\/3).","volume":"157","author":"CL Trimble","year":"2020","journal-title":"Gynecol Oncol"},{"issue":"3","key":"pone.0295647.ref013","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/DCR.0000000000000991","article-title":"A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra-anal 5% Imiquimod in HIV-1-Infected Men With High-Grade Squamous Intraepithelial Lesions","volume":"61","author":"RD Cranston","year":"2018","journal-title":"Dis Colon Rectum"},{"issue":"4","key":"pone.0295647.ref014","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S1470-2045(13)70067-6","article-title":"Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial.","volume":"14","author":"O Richel","year":"2013","journal-title":"Lancet Oncol."},{"issue":"2","key":"pone.0295647.ref015","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1177\/1545109710382578","article-title":"Initial Experience with Topical Fluorouracil for Treatment of HIV-Associated Anal Intraepithelial Neoplasia.","volume":"10","author":"SM Snyder","year":"2011","journal-title":"J Int Assoc Physicians AIDS Care (Chic)."},{"issue":"10","key":"pone.0295647.ref016","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1177\/0956462419855828","article-title":"Intra-anal use of imiquimod: what is the clinical evidence","volume":"30","author":"ID Gkegkes","year":"2019","journal-title":"Int J STD AIDS"},{"issue":"18","key":"pone.0295647.ref017","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1111\/j.1742-4658.2007.05999.x","article-title":"Drug-resistant malaria\u2014an insight.","volume":"274","author":"JE Hyde","year":"2007","journal-title":"FEBS J."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T18:38:53Z","timestamp":1702665533000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295647"}},"subtitle":[],"editor":[{"given":"Diane M.","family":"Harper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":17,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0295647","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]}}}