A phase II study of Yondelis® (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer
Open Access
- 30 May 2006
- journal article
- research article
- Published by Springer Nature in British Journal of Cancer
- Vol. 94 (11) , 1610-1614
- https://doi.org/10.1038/sj.bjc.6603142
Abstract
Yondelis® (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m−2 was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36–67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88–15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.Keywords
This publication has 14 references indexed in Scilit:
- Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naïve patientsMolecular Cancer Therapeutics, 2005
- Preclinical and clinical results with the natural marine product ET-743.2003
- Preclinical and clinical results with the natural marine product ET-743Expert Opinion on Investigational Drugs, 2003
- The combination of yondelis and cisplatin is synergistic against human tumor xenograftsEuropean Journal Of Cancer, 2003
- Effective combination of ET-743 and doxorubicin in sarcoma: preclinical studiesCancer Chemotherapy and Pharmacology, 2003
- Sequence-dependent synergistic cytotoxicity of ecteinascidin-743 and paclitaxel in human breast cancer cell lines in vitro and in vivo.2002
- Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743.2002
- Unique Features of the Mode of Action of ET-743The Oncologist, 2002
- Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repairNature Medicine, 2001
- Progress in the acquisition of new marine-derived anticancer compounds: development of ecteinascidin-743 (ET-743)Drugs of the Future, 1996