{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:59:31Z","timestamp":1778878771399,"version":"3.51.4"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patient data for multiple cardiac\u2010related treatment\u2010emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase\u00a02 trials, one phase 3 trial in STS (<jats:italic>n<\/jats:italic>\u00a0=\u00a0982), and two phase 3 trials in ROC (<jats:italic>n<\/jats:italic>\u00a0=\u00a01231).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multivariate analyses on pooled trabectedin data revealed that cardiovascular medical history (risk ratio [RR (95% CI)]: 1.90 [1.24\u20102.91]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.003) and age \u226565\u00a0years (RR [95% CI]: 1.78 [1.12\u20102.83]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.014) were associated with increased risk for cTEAEs. Multivariate analyses showed increased risk of experiencing cTEAEs with T+PLD compared to PLD monotherapy (RR [95% CI]: 2.70 [1.75\u20104.17]; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001) and with history of prior cardiac medication (RR [95% CI]: 1.88 [1.16\u20103.05]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.010).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>For patients with STS or ROC who still have limited treatment options, trabectedin may be initiated after carefully considering benefit versus risk.<\/jats:p><jats:p><jats:bold>Trial Registration<\/jats:bold> (ClinicalTrials.gov): NCT01343277; NCT00113607; NCT01846611.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3903","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T23:00:38Z","timestamp":1620514838000},"page":"3565-3574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-3844","authenticated-orcid":false,"given":"Robin L.","family":"Jones","sequence":"first","affiliation":[{"name":"Sarcoma Unit Royal Marsden Hospital\/Institute of Cancer Research London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Herzog","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center University of Cincinnati Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-2348","authenticated-orcid":false,"given":"Shreyaskumar R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Sarcoma Medical Oncology University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-890X","authenticated-orcid":false,"given":"Margaret","family":"von Mehren","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Schuetze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-6668","authenticated-orcid":false,"given":"Brian A.","family":"Van Tine","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-8754","authenticated-orcid":false,"given":"Robert L.","family":"Coleman","sequence":"additional","affiliation":[{"name":"US Oncology Research The Woodlands TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Knoblauch","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Raritan NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spyros","family":"Triantos","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Raritan NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hu","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Raritan NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleed","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Medical Group Oncology Janssen Scientific Affairs, LLC Horsham PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"McGowan","sequence":"additional","affiliation":[{"name":"Medical Group Oncology Janssen Scientific Affairs, LLC Horsham PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley J.","family":"Monk","sequence":"additional","affiliation":[{"name":"Arizona Oncology (US Oncology Network) University of Arizona College of Medicine, and Creighton University School of Medicine at St. Joseph's Hospital and Medical Center Phoenix AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George D.","family":"Demetri","sequence":"additional","affiliation":[{"name":"Sarcoma Center Department of Medical Oncology Dana\u2010Farber Cancer Institute (DFCI) Harvard Medical School and Ludwig Center at Harvard Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-015-2918-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1614-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.62.4734"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.4037"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.12.043"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.462"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0901"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6775"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6780"},{"key":"e_1_2_10_11_1","volume-title":"Doxil [prescribing information]","year":"2010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1292"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/suz230"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3903","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.3903","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3903","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T06:37:35Z","timestamp":1693377455000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.3903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":12,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/cam4.3903"],"URL":"https:\/\/doi.org\/10.1002\/cam4.3903","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]},"assertion":[{"value":"2020-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}