{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:39:34Z","timestamp":1791527974250,"version":"4.3.4"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"GlaxoSmithKline Pharmaceuticals, Philadelphia, PA."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose.<\/jats:title>\n                    <jats:p>To evaluate the maximum tolerated regimen (MTR), dose-limiting toxicities, and pharmacokinetics of pazopanib, an oral small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit, in combination with paclitaxel.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods.<\/jats:title>\n                    <jats:p>Pazopanib was given daily with weekly paclitaxel on days 1, 8, and 15 every 28 days. Dose levels of pazopanib (mg\/day)\/paclitaxel (mg\/m2) were 400\/15, 800\/15, 800\/50, and 800\/80. An expanded cohort was enrolled at the MTR. Plasma samples were collected to evaluate the effect of pazopanib, an inhibitor of cytochrome P450 (CYP)3A4, on the pharmacokinetics of paclitaxel, a CYP3A4 and CYP2C8 substrate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results.<\/jats:title>\n                    <jats:p>Of 26 enrolled patients, 17 were treated at the MTR of 800 mg pazopanib and 80 mg\/m2 paclitaxel. Dose-limiting toxicities included a grade 3 abscess and grade 2 hyperbilirubinemia. Other toxicities included elevated liver transaminases and diarrhea. Six patients (23%) had partial responses and 15 patients (58%) had stable disease. Administration of 800 mg pazopanib resulted in a 14% lower paclitaxel clearance and a 31% higher paclitaxel maximal concentration than with administration of paclitaxel alone at 15, 50, and 80 mg\/m2. At the MTR, coadministration of 800 mg pazopanib and 80 mg\/m2 paclitaxel resulted in a 26% higher geometric mean paclitaxel area under the curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion.<\/jats:title>\n                    <jats:p>Pazopanib, at a dose of 800 mg daily, can be safely combined with a therapeutic dose of paclitaxel at 80 mg\/m2 when administered on days 1, 8, and 15, every 28 days. The observed greater plasma concentrations of paclitaxel given concurrently with pazopanib suggest that pazopanib is a weak inhibitor of CYP3A4 and CYP2C8.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2010-0095","type":"journal-article","created":{"date-parts":[[2010,12,8]],"date-time":"2010-12-08T21:03:22Z","timestamp":1291842202000},"page":"1253-1261","source":"Crossref","is-referenced-by-count":37,"title":["Phase I Study of Pazopanib in Combination with Weekly Paclitaxel in Patients with Advanced Solid Tumors"],"prefix":"10.1093","volume":"15","author":[{"given":"Antoinette R.","family":"Tan","sequence":"first","affiliation":[{"name":"a The Cancer Institute of New Jersey, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Dowlati","sequence":"additional","affiliation":[{"name":"b University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne F.","family":"Jones","sequence":"additional","affiliation":[{"name":"c Sarah Cannon Research Institute, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Infante","sequence":"additional","affiliation":[{"name":"c Sarah Cannon Research Institute, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Nishioka","sequence":"additional","affiliation":[{"name":"a The Cancer Institute of New Jersey, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fang","sequence":"additional","affiliation":[{"name":"d GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Hodge","sequence":"additional","affiliation":[{"name":"d GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby D.","family":"Gainer","sequence":"additional","affiliation":[{"name":"d GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thangam","family":"Arumugham","sequence":"additional","affiliation":[{"name":"d GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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