A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer
Open Access
- 30 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in International Journal of Clinical Oncology
- Vol. 26 (10), 1977-1985
- https://doi.org/10.1007/s10147-021-01973-1
Abstract
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-163164Keywords
Funding Information
- Taiho Pharmaceutical
This publication has 14 references indexed in Scilit:
- Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upAnnals of Oncology, 2013
- Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian CancerJournal of Clinical Oncology, 2010
- Dose Escalation Methods in Phase I Cancer Clinical TrialsJNCI Journal of the National Cancer Institute, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Phase II Clinical Trial of Pegylated Liposomal Doxorubicin (JNS002) in Japanese Patients with Mullerian Carcinoma (Epithelial Ovarian Carcinoma, Primary Carcinoma of Fallopian Tube, Peritoneal Carcinoma) Having a Therapeutic History of Platinum-based Chemotherapy: A Phase II Study of the Japanese Gynecologic Oncology GroupJapanese Journal of Clinical Oncology, 2008
- A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimensBritish Journal of Cancer, 2007
- Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian CancerJournal of Clinical Oncology, 2007
- Pegylated liposomal doxorubicin and vinorelbine in recurrent ovarian carcinoma: a pharmacokinetic study on alternate administration sequences.2006
- The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancerGynecologic Oncology, 2006
- Pharmacokinetics of Pegylated Liposomal DoxorubicinClinical Pharmacokinetics, 2003