Annals of Oncology Advance Access published online on June 25, 2009
Annals of Oncology, doi:10.1093/annonc/mdp198
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Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer
1 Department of Medical Oncology, Vall d'Hebrón University Hospital, Barcelona, Spain
2 Wielkopolska Oncology Center, Poznan
3 Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland
4 Ion Chiricuta Cancer Institute, Cluj Napoca, Romania
5 Department of Gynecologic Oncology, University Hospital, Linköping, Sweden
6 Comprehensive Cancer Center of Bialystok and Department of Oncology, Medical University, Bialystok, Poland
7 Department of Medical Oncology, Valencian Institute of Oncology, Valencia, Spain
8 Department of Gynecological Oncology, University Hospital Umea, Sweden
9 Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
10 PharmaMar Clinical R&D, Colmenar Viejo, Spain
* Correspondence to: Dr J. M. Del Campo, Department of Medical Oncology, Vall d'Hebrón University Hospital , Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. Tel: +34-93-274-61 32; Fax: +34-93-274-6059; E-mail: jmcampo{at}vhebron.net
Background: This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC).
Patients and methods: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m2 24 h (arm A, n = 54) or 1.3 mg/m2 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute—Common Toxicity Criteria v. 2.0.
Results: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3–8.6 months; arm A) and 6.8 months (95% CI 4.6–7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B).
Conclusions: Both every-3-weeks trabectedin regimes, 1.5 mg/m2 24 h and 1.3 mg/m2 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.
ovarian cancer, phase II, RECIST, response rate, trabectedin
Received for publication December 17, 2008. Revision received March 3, 2009. Accepted for publication March 4, 2009.