{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:15:04Z","timestamp":1792088104014,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1 ZIA BC011286 05"],"award-info":[{"award-number":["1 ZIA BC011286 05"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adrenocortical carcinoma (<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>) is a rare but lethal malignancy without effective current therapy for metastatic disease. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> is a recombinant cytotoxin consisting of human interleukin\u201013 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013) and a truncated form of <jats:italic>Pseudomonas<\/jats:italic> exotoxin A (<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>). The main objectives of this Phase I dose\u2010escalation trial were to assess the maximum\u2010tolerated dose (<jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>), safety, and pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> in patients with metastatic <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>. Eligible patients had confirmed <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 receptor alpha 2 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R<jats:italic>\u03b1<\/jats:italic>2) expressions in their tumors. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> at dose of 1\u20132\u00a0<jats:italic>\u03bc<\/jats:italic>g\/kg was administered intravenously (<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>) on day 1, 3, and 5 in a 4\u2010week cycle. Six patients received 1\u00a0<jats:italic>\u03bc<\/jats:italic>g\/kg and two patients received 2\u00a0<jats:italic>\u03bc<\/jats:italic>g\/kg of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>. Dose\u2010limiting toxicity was observed at 2\u00a0<jats:italic>\u03bc<\/jats:italic>g\/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> analysis demonstrated that at <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>, the mean maximum serum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> was 21.0\u00a0ng\/mL, and the terminal half\u2010life of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> was 30\u201339\u00a0min. Two (25%) of the eight patients had baseline neutralizing antibodies against <jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>. Three (75%) of the remaining four tested patients developed neutralizing antibodies against <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> within 14\u201328\u00a0days of initial treatment. Of the five patients treated at <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content> and assessed for response, one patient had stable disease for 5.5\u00a0months before disease progression; the others progressed within 1\u20132\u00a0months. In conclusion, systemic <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> administration of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> is safe at 1\u00a0<jats:italic>\u03bc<\/jats:italic>g\/kg. All tested patients developed high levels of neutralizing antibodies during <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> treatment. Use of strategies for immunodepletion before <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content> treatment should be considered in future trials.<\/jats:p>","DOI":"10.1002\/cam4.449","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T10:19:08Z","timestamp":1426241948000},"page":"1060-1068","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Phase I trial of systemic intravenous infusion of interleukin\u201013\u2010<i>Pseudomonas<\/i> exotoxin in patients with metastatic adrenocortical carcinoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Yi","family":"Liu\u2010Chittenden","sequence":"first","affiliation":[{"name":"Endocrine Oncology Branch National Cancer Institute, National Institutes of Health Bethesda 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