Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer
Mené sur trois cohortes de patients atteints d'un cancer métastatique de la prostate résistant à la castration (total : 58 patients), cet essai de phase II évalue l'efficacité et la toxicité du trabectedine selon trois protocoles d'administration du traitement
Background: This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC).Patients and methods: Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m2 (Cohort B1, n = 5) and 1.2 mg/m2 (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP).Results: Trabectedin resulted in PSA declines ≥50% in 12.5% (Cohort A) and 10.5% (Cohort B2) of patients. Among men pretreated with taxane-based chemotherapy, PSA response was 13.6% (Cohort A) and 15.4% (Cohort B2). PSA responses lasted 4.1–8.6 months, and median TTP was 1.5 months (Cohort A) and 1.9 months (Cohort B2). The dose of 1.5 mg/m2 (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m2 q3wk and 0.58 mg/m2 weekly, the most common adverse events were nausea, fatigue and transient neutropenia and transaminase increase.Conclusions: Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer.
Annals of Oncology 2011