British Journal of Cancer (2006) 94, 1610-1614.
doi:10.1038/sj.bjc.6603142
A phase II study of YondelisÒ (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer
L Zelek1,2, A Yovine3, E Brain4, F Turpin4, A Taamma5, M Riofrio1, M Spielmann1, J Jimeno6 and J L Misset3
1Department of Medicine, Institut Gustave-Roussy, Villejuif, France
2Department of Medical Oncology, Henri Mondor Hospital, Créteil Cedex, France
3Service d'Oncologie, Hôpital Paul-Brousse, Villejuif, France
4Department of Medicine, Centre René-Huguenin, Saint-Cloud, France
5Cvitkovic and Associates, Kremlin-Bicêtre, France
6PharmaMar R&D, Madrid, Spain
Correspondence to: Dr L Zelek, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier Hospital, Department of Medical Oncology, 51 avenue du Maréchal Delattre de Tassigny, Créteil Cedex 94010, France. E-mail: laurent.zelek@hmn.aphp.fr
Received 1 February 2006; revised 3 April 2006; accepted 3 April 2006
YondelisÒ (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.