{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T04:05:44Z","timestamp":1747454744900,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Paclitaxel is an antimitotic agent that targets elements of the cancer phenotype, including cell proliferation, DNA repair, and apoptosis, predicting its broad activity in a spectrum of cancers. An oral paclitaxel formulation has been developed to overcome challenges associated with parenteral administration of this drug, notably the development of Cremophor\u2010induced acute hypersensitivity reactions, which are particularly problematic in dogs. The aim of this open\u2010label, dose\u2010escalating study was to evaluate the tolerability and determine the maximum tolerated dosage (MTD) and dose\u2010limiting toxicity (DLT) of oral paclitaxel when co\u2010administered with the P\u2010glycoprotein pump inhibitor, encequidar, in dogs with cancer. Paclitaxel was administered as a 3\u2010consecutive\u2010day course starting at 90\u2009mg\/m<jats:sup>2<\/jats:sup> with encequidar weekly for 3\u2009weeks, using escalation of 30\u2009mg\/m<jats:sup>2<\/jats:sup> increments. MTD was established using a rolling\u2010six dose escalation study design, based on the number of dogs experiencing any DLT assessed after each dosing cycle and during a 28\u2010day post\u2010treatment monitoring period. Nineteen client\u2010owned dogs were enrolled. MTD was established at 90\u2009mg\/m<jats:sup>2<\/jats:sup> and the most frequent adverse events (AEs) were gastrointestinal, followed by hematologic, with the majority being self\u2010resolving and low grade. VCOG Grades 3 and 4 gastrointestinal toxicity, Grade 4 neutropenia, and acute kidney injury were defined as DLTs at 120\u2009mg\/m<jats:sup>2<\/jats:sup>. Conclusions of this study define oral paclitaxel MTD in cancer\u2010bearing dogs at 90\u2009mg\/m<jats:sup>2<\/jats:sup> when given with encequidar for 3 consecutive days weekly for 3\u2009weeks. Future Phase 2 trials evaluating the therapeutic activity of oral paclitaxel at its MTD co\u2010administered with encequidar in defined tumour histologies are warranted.<\/jats:p>","DOI":"10.1111\/vco.13045","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:54:45Z","timestamp":1741733685000},"page":"197-204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tolerability Assessment of Orally Administered Paclitaxel With Encequidar in Dogs With Spontaneous Malignancy"],"prefix":"10.1111","volume":"23","author":[{"given":"Jordan","family":"Ziegler","sequence":"first","affiliation":[{"name":"Veterinary Specialty Hospital of san Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2993-5179","authenticated-orcid":false,"given":"Jacob","family":"Cawley","sequence":"additional","affiliation":[{"name":"Ethos Discovery  San Diego California USA"},{"name":"Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Istvan","sequence":"additional","affiliation":[{"name":"Veterinary Specialty Hospital of san Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saya","family":"Press","sequence":"additional","affiliation":[{"name":"Veterinary Specialty Hospital of san Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Stewart","sequence":"additional","affiliation":[{"name":"Ethos Discovery  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chand","family":"Khanna","sequence":"additional","affiliation":[{"name":"Ethos Discovery  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joelle","family":"Fenger","sequence":"additional","affiliation":[{"name":"Ethos Discovery  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12596"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)41836-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/277665a0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.3.1561"},{"key":"e_1_2_8_6_1","first-page":"S19\u201011","article-title":"Paclitaxel Pharmacology and Other Tumor Types","volume":"24","author":"Rowinsky E. 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