A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

Shunji Takahashi, Munetaka Takekuma, Kenji Tamura, Kazuhiro Takehara, Hiroyuki Nomura, Makiko Ono, Mayu Yunokawa, Daisuke Aoki

研究成果: Article査読

抄録

Background: Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods: 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 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days 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. Results: Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 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%. Conclusions: 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 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

本文言語English
ページ(範囲)1977-1985
ページ数9
ジャーナルInternational Journal of Clinical Oncology
26
10
DOI
出版ステータスPublished - 2021 10

ASJC Scopus subject areas

  • 外科
  • 血液学
  • 腫瘍学

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