{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:15:35Z","timestamp":1776813335510,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013119","name":"PharmaMar","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013119","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although elderly patients (\u226570 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline\u2010based chemotherapy. Trabectedin is registered as a second\u2010line treatment for advanced STS and is characterized by a favorable safety profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The aim of this single\u2010arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3\u20101.5 mg\/m<jats:sup>2<\/jats:sup>) as a first\u2010line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline\u2010based chemotherapy. The coprimary endpoints were progression\u2010free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74\u201083 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3\u20106), with 7 patients (29%) receiving \u22656 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3\/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%\u201081%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%\u201057%]) experienced CLTs. Trabectedin C<jats:sub>max<\/jats:sub>, half\u2010life, clearance, and distribution volume were 1.28 ng\/mL (standard deviation [SD], 0.58 ng\/mL), 26.70 hours (SD, 9.09 hours), 39.98 L\/h\/m<jats:sup>2<\/jats:sup> (SD, 14.08 L\/h\/m<jats:sup>2<\/jats:sup>), and 1460 L\/m<jats:sup>2<\/jats:sup> (SD, 561 L\/m<jats:sup>2<\/jats:sup>), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33120","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T11:02:39Z","timestamp":1596538959000},"page":"4726-4734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pharmacokinetics, safety, and activity of trabectedin as first\u2010line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group"],"prefix":"10.1002","volume":"126","author":[{"given":"Federica","family":"Grosso","sequence":"first","affiliation":[{"name":"Mesothelioma and Rare Cancer Unit Azienda Ospedaliera SS Antonio e Biagio General Hospital Alessandria Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Candiolo Cancer Institute, FPO\u2013IRCCS Candiolo Italy"},{"name":"Department of Oncology University of Torino Orbassano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Zucchetti","sequence":"additional","affiliation":[{"name":"Department of Oncology Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Osteoncology and Rare Tumors Center Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Tamberi","sequence":"additional","affiliation":[{"name":"Oncology Unit Ospedale Per Gli Infermi Faenza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Matteo","sequence":"additional","affiliation":[{"name":"Department of Oncology Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-4137","authenticated-orcid":false,"given":"Eliana","family":"Rulli","sequence":"additional","affiliation":[{"name":"Department of Oncology Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danila","family":"Comandini","sequence":"additional","affiliation":[{"name":"Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Palmerini","sequence":"additional","affiliation":[{"name":"Chemoterapy Unit IRCCS Istituto Ortopedico Rizzoli Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo Giulio","family":"Baldi","sequence":"additional","affiliation":[{"name":"Medical Oncology Department \u201cSanto Stefano\u201d Hospital Prato Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"DeCensi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Unit EO Ospedali Galliera Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Bergaglio","sequence":"additional","affiliation":[{"name":"Oncology Unit Villa Scassi Hospital, ASL3 Genovese Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Marra","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Unit EO Ospedali Galliera Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Candiolo Cancer Institute, FPO\u2013IRCCS Candiolo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Siri","sequence":"additional","affiliation":[{"name":"Department of Mathematics University of Genoa Genova Italy"},{"name":"E.O. 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