{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:35:26Z","timestamp":1793968526031,"version":"4.8.0"},"reference-count":15,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Intravenous paclitaxel (IVpac) is complicated by neuropathy and requires premedication to prevent hypersensitivity-type reactions. Paclitaxel is poorly absorbed orally; encequidar (E), a novel P-glycoprotein pump inhibitor, allows oral absorption. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> A phase III open-label study comparing oral paclitaxel plus E (oPac + E) 205 mg\/m<jats:sup>2<\/jats:sup> paclitaxel plus 15 mg E methanesulfonate monohydrate 3 consecutive days per week versus IVpac 175 mg\/m<jats:sup>2<\/jats:sup> once every 3 weeks was performed. Women with metastatic breast cancer and adequate organ function, at least 1 year from last taxane, were randomly assigned 2:1 to oPac + E versus IVpac. The primary end point was confirmed radiographic response using RECIST 1.1, assessed by blinded independent central review. Secondary end points included progression-free survival (PFS) and overall survival (OS). <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Four hundred two patients from Latin America were enrolled (265 oPac + E, 137 IVpac); demographics and prior therapies were balanced. The confirmed response (intent-to-treat) was 36% for oPac + E versus 23% for IVpac ( P = .01). The PFS was 8.4 versus 7.4 months, respectively (hazard ratio, 0.768; 95.5% CI, 0.584 to 1.01; P = .046), and the OS was 22.7 versus 16.5 months, respectively (hazard ratio, 0.794; 95.5% CI, 0.607 to 1.037; P = .08). Grade 3-4 adverse reactions were 55% with oPac + E and 53% with IVpac. oPac + E had lower incidence and severity of neuropathy (2% v 15% &gt; grade 2) and alopecia (49% v 62% all grades) than IVpac but more nausea, vomiting, diarrhea, and neutropenic complications, particularly in patients with elevated liver enzymes. On-study deaths (8% oPac + E v 9% IVpac) were treatment-related in 3% and 0%, respectively. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> oPac + E increased the confirmed tumor response versus IVpac, with trends in PFS and OS. Neuropathy was less frequent and severe with oPac + E; neutropenic serious infections were increased. Elevated liver enzymes at baseline predispose oPac + E patients to early neutropenia and serious infections (funded by Athenex, Inc; ClinicalTrials.gov identifier: NCT02594371 ). <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.02953","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T19:59:30Z","timestamp":1658347170000},"page":"65-74","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct02594371","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6710-4814","authenticated-orcid":false,"given":"Hope S.","family":"Rugo","sequence":"first","affiliation":[{"name":"University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-706X","authenticated-orcid":false,"given":"Gerardo A.","family":"Umanzor","sequence":"additional","affiliation":[{"name":"Centro Oncol\u00f3gico Integral with DEMEDICA, San Pedro Sula, Honduras"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Barrios","sequence":"additional","affiliation":[{"name":"American Cancer Center, Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9964-5778","authenticated-orcid":false,"given":"Rosa H.","family":"Vasallo","sequence":"additional","affiliation":[{"name":"Clinical Research RD, Santo Domingo, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Chivalan","sequence":"additional","affiliation":[{"name":"CELAN Cl\u00ednica M\u00e9dica, Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-1342","authenticated-orcid":false,"given":"Suyapa","family":"Bejarano","sequence":"additional","affiliation":[{"name":"Excel Medica, San Pedro Sula, Honduras"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio R.","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Sanatorio Centro Regional de Sub-Especialidades M\u00e9dicas (CRESEM), Quetzaltenango, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-1346","authenticated-orcid":false,"given":"Luis","family":"Fein","sequence":"additional","affiliation":[{"name":"Instituto de Oncolog\u00eda de Rosario, Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben D.","family":"Kowalyszyn","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cl\u00ednicas, Cl\u00ednica Viedma, Viedma, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Douglas","family":"Kramer","sequence":"additional","affiliation":[{"name":"Athenex, Inc, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Athenex, Inc, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Fun R.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Athenex, Inc, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-1082","authenticated-orcid":false,"given":"David L.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Athenex, Inc, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Oraxol Study Consortium Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","first-page":"159","volume":"6","author":"Gradishar WJ","year":"2012","journal-title":"Breast Cancer (Auckl)"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2607-5"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-199714050-00011"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.6699"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707056"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.0308"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx162"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0391-z"},{"key":"b9","first-page":"465","volume":"28","author":"Dodd MJ","year":"2001","journal-title":"Oncol Nurs Forum"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.41.7238"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S106629"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.2031"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz244.039"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.1084"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.937"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.21.02953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T23:00:26Z","timestamp":1671750026000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.02953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"alternative-id":["10.1200\/JCO.21.02953"],"URL":"https:\/\/doi.org\/10.1200\/jco.21.02953","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,1]]},"assertion":[{"value":"2021-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-09","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}