Annals of Oncology Advance Access originally published online on June 25, 2009
Annals of Oncology 2009 20(11):1794-1802; doi:10.1093/annonc/mdp198
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gynecologic tumors |
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.
Key words: 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.