{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:35:46Z","timestamp":1791214546735,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We assessed the activity of sorafenib plus metronomic paclitaxel as second\/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Multicenter, prospective phase II trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Referral centers for ACC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60\u200amg\/m<jats:sup>2<\/jats:sup> every week) and oral sorafenib (400\u200amg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the <jats:italic>in vitro<\/jats:italic> study, sorafenib impaired the viability of H295R cells with dose\u2013response and time\u2013response relationships. The <jats:italic>in vitro<\/jats:italic> sorafenib activity was not increased in combination with paclitaxel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite the <jats:italic>in vitro<\/jats:italic> activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-11-0918","type":"journal-article","created":{"date-parts":[[2011,12,22]],"date-time":"2011-12-22T05:10:47Z","timestamp":1324530647000},"page":"451-458","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":128,"title":["Phase II study of weekly paclitaxel and sorafenib as second\/third-line therapy in patients with adrenocortical carcinoma"],"prefix":"10.1093","volume":"166","author":[{"given":"Alfredo","family":"Berruti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Sperone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ferrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina","family":"Germano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Ardito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano Massimiliano","family":"Priola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"De Francia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Volante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvia","family":"Daffara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Generali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Leboulleux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Perotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Baudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Papotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Terzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"2","key":"1_16175097","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0039-6060(96)80164-4","volume":"119","author":"Crucitti","year":"1996","journal-title":"Surgery","ISSN":"https:\/\/id.crossref.org\/issn\/0039-6060","issn-type":"print"},{"issue":"6","key":"2_21809127","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1210\/jc.2005-2639","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1","key":"3_22874431","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1210\/jc.2006-0706","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"3","key":"4_31849682","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1517\/14728214.13.3.497","volume":"13","author":"Berruti","year":"2008","journal-title":"Expert opinion on emerging drugs","ISSN":"https:\/\/id.crossref.org\/issn\/1472-8214","issn-type":"print"},{"issue":"6","key":"5_18203962","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nrc1369","volume":"4","author":"Kerbel","year":"2004","journal-title":"Nature reviews. 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