{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:20:50Z","timestamp":1772310050946,"version":"3.50.1"},"reference-count":37,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"am","delay-in-days":374,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["3U01CA069856-15S1"],"award-info":[{"award-number":["3U01CA069856-15S1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinical-genitourinary-cancer.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genitourinary Cancer"],"published-print":{"date-parts":[[2020,6]]},"DOI":"10.1016\/j.clgc.2019.10.013","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T19:57:21Z","timestamp":1578686241000},"page":"171-178.e2","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Phase I Trial of IGF-1R Inhibitor Cixutumumab and mTOR Inhibitor Temsirolimus in Metastatic Castration-resistant Prostate Cancer"],"prefix":"10.1016","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1477-0105","authenticated-orcid":false,"given":"Deaglan J.","family":"McHugh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Chudow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"DeNunzio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan F.","family":"Slovin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Danila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard I.","family":"Scher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana E.","family":"Rathkopf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.clgc.2019.10.013_bib1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Clin J Clin"},{"key":"10.1016\/j.clgc.2019.10.013_bib2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib3","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1014618","article-title":"Abiraterone and increased survival in metastatic prostate cancer","volume":"364","author":"de Bono","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1213755","article-title":"Alpha emitter radium-223 and survival in metastatic prostate cancer","volume":"369","author":"Parker","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib5","first-page":"767","article-title":"Abiraterone and increased survival in metastatic prostate cancer","volume":"365","author":"Parker","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib6","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJMoa1207506","article-title":"Increased survival with enzalutamide in prostate cancer after chemotherapy","volume":"367","author":"Scher","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib7","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/j.1742-1241.2011.02799.x","article-title":"Characterising the castration-resistant prostate cancer population: a systematic review","volume":"65","author":"Kirby","year":"2011","journal-title":"Int J Clin Pract"},{"key":"10.1016\/j.clgc.2019.10.013_bib8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ccr.2010.05.026","article-title":"Integrative genomic profiling of human prostate cancer","volume":"18","author":"Taylor","year":"2010","journal-title":"Cancer Cell"},{"key":"10.1016\/j.clgc.2019.10.013_bib9","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","article-title":"Integrative clinical genomics of advanced prostate cancer","volume":"161","author":"Robinson","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.clgc.2019.10.013_bib10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.clgc.2013.05.007","article-title":"A\u00a0phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer","volume":"11","author":"Armstrong","year":"2013","journal-title":"Clin Genitourin Cancer"},{"key":"10.1016\/j.clgc.2019.10.013_bib11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.eururo.2013.03.040","article-title":"Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08\/08)","volume":"64","author":"Templeton","year":"2013","journal-title":"Eur Urol"},{"key":"10.1016\/j.clgc.2019.10.013_bib12","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt","volume":"66","author":"O'Reilly","year":"2006","journal-title":"Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib13","doi-asserted-by":"crossref","first-page":"7052","DOI":"10.1158\/0008-5472.CAN-05-0917","article-title":"Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition","volume":"65","author":"Sun","year":"2005","journal-title":"Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib14","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1038\/sj.onc.1209990","article-title":"Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism","volume":"26","author":"Wan","year":"2007","journal-title":"Oncogene"},{"issue":"suppl","key":"10.1016\/j.clgc.2019.10.013_bib15","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1200\/jco.2009.27.15_suppl.5142","volume":"27","author":"Higano","year":"2009","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.clgc.2019.10.013_bib16","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrc1974","article-title":"mTOR and cancer: insights into a complex relationship","volume":"6","author":"Sabatini","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.clgc.2019.10.013_bib17","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1158\/1078-0432.CCR-10-2979","article-title":"Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer","volume":"17","author":"Naing","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib18","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1158\/1078-0432.CCR-12-0061","article-title":"Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors","volume":"18","author":"Naing","year":"2012","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib19","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/bjc.2013.46","article-title":"Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma","volume":"108","author":"Naing","year":"2013","journal-title":"Br J Cancer"},{"key":"10.1016\/j.clgc.2019.10.013_bib20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2967\/jnumed.109.066159","article-title":"Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET","volume":"51","author":"Beattie","year":"2010","journal-title":"J\u00a0Nucl Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s00259-005-1764-5","article-title":"Positron tomographic assessment of androgen receptors in prostatic carcinoma","volume":"32","author":"Dehdashti","year":"2005","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.1016\/j.clgc.2019.10.013_bib22","first-page":"366","article-title":"Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer","volume":"45","author":"Larson","year":"2004","journal-title":"J\u00a0Nucl Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib23","first-page":"1966","article-title":"PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer","volume":"45","author":"Zanzonico","year":"2004","journal-title":"J\u00a0Nucl Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib24","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/S0140-6736(10)60172-9","article-title":"Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study","volume":"375","author":"Scher","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.clgc.2019.10.013_bib25","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.2967\/jnumed.111.089326","article-title":"Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET\/CT","volume":"52","author":"Fox","year":"2011","journal-title":"J\u00a0Nucl Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib26","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1158\/1078-0432.CCR-07-1506","article-title":"Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer","volume":"13","author":"Danila","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib27","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1200\/JCO.2007.12.4487","article-title":"Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group","volume":"26","author":"Scher","year":"2008","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.clgc.2019.10.013_bib28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/jnci\/92.3.205","article-title":"New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada","volume":"92","author":"Therasse","year":"2000","journal-title":"J\u00a0Natl Cancer Inst"},{"key":"10.1016\/j.clgc.2019.10.013_bib29","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1158\/1078-0432.CCR-13-0231","article-title":"Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer","volume":"19","author":"Tagawa","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.clgc.2019.10.013_bib30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10549-013-2528-8","article-title":"A\u00a0phase I trial of the IGF-1R antibody cixutumumab in combination with temsirolimus in patients with metastatic breast cancer","volume":"139","author":"Ma","year":"2013","journal-title":"Breast Cancer Res Treat"},{"key":"10.1016\/j.clgc.2019.10.013_bib31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1470-2045(13)70049-4","article-title":"Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial","volume":"14","author":"Schwartz","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clgc.2019.10.013_bib32","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1164\/rccm.200911-1720OC","article-title":"Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma","volume":"182","author":"White","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib33","doi-asserted-by":"crossref","first-page":"C836","DOI":"10.1152\/ajpcell.00554.2007","article-title":"A\u00a0GSK-3\/TSC2\/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression","volume":"295","author":"Buller","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.clgc.2019.10.013_bib34","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ccr.2011.04.008","article-title":"Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer","volume":"19","author":"Carver","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1016\/j.clgc.2019.10.013_bib35","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.molmed.2007.08.001","article-title":"Targeting the mTOR signaling network in cancer","volume":"13","author":"Chiang","year":"2007","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.clgc.2019.10.013_bib36","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1517\/13543784.2011.541154","article-title":"Current and future directions in mammalian target of rapamycin inhibitors development","volume":"20","author":"Fasolo","year":"2011","journal-title":"Exp Opin Invest Drugs"},{"key":"10.1016\/j.clgc.2019.10.013_bib37","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1158\/1078-0432.CCR-18-0981","article-title":"Randomized phase II study evaluating Akt blockade with ipatasertib, in combination with abiraterone, in patients with metastatic prostate cancer with and without PTEN loss","volume":"25","author":"de Bono","year":"2019","journal-title":"Clin Cancer Res"}],"container-title":["Clinical Genitourinary Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1558767319303179?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1558767319303179?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T11:32:38Z","timestamp":1761564758000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1558767319303179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["S1558767319303179"],"URL":"https:\/\/doi.org\/10.1016\/j.clgc.2019.10.013","relation":{},"ISSN":["1558-7673"],"issn-type":[{"value":"1558-7673","type":"print"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Phase I Trial of IGF-1R Inhibitor Cixutumumab and mTOR Inhibitor Temsirolimus in Metastatic Castration-resistant Prostate Cancer","name":"articletitle","label":"Article Title"},{"value":"Clinical Genitourinary Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clgc.2019.10.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}