{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:16:16Z","timestamp":1740107776416,"version":"3.37.3"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009954","name":"Taiho Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009954","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1\u00a0mg\/m<jats:sup>2<\/jats:sup> immediately after PLD 30\u00a0mg\/m<jats:sup>2<\/jats:sup>; both drugs were given by intravenous infusion. Treatment was repeated every 21\u00a0days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Eighteen patients were included. The MTD of trabectedin was determined as 1.1\u00a0mg\/m<jats:sup>2<\/jats:sup>. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade\u2009\u2265\u20093 elevations in transaminase levels or grade\u2009\u2265\u20093 reductions in neutrophil count, but these events were generally manageable through dose reduction and\/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1\u00a0mg\/m<jats:sup>2<\/jats:sup> once every 21\u00a0days.<\/jats:p>\n                <jats:p><jats:italic>Clinical trial registration number<\/jats:italic>: JapicCTI-163164<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10147-021-01973-1","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T02:03:05Z","timestamp":1625018585000},"page":"1977-1985","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer"],"prefix":"10.1007","volume":"26","author":[{"given":"Shunji","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munetaka","family":"Takekuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayu","family":"Yunokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-8326","authenticated-orcid":false,"given":"Daisuke","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"1973_CR1","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1158\/1055-9965.EPI-16-0858","volume":"26","author":"LA Torre","year":"2017","unstructured":"Torre LA, Islami F, Siegel RL et al (2017) Global cancer in women: burden and trends. 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Kenji Tamura has received research funding from Eisai, Pfizer, AstraZeneca, Eli Lilly, and Daiichi Sankyo. Kazuhiro Takehara has received honoraria from AstraZeneca. All other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}