Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer

• Published in: Annals of oncology Vol. 23; no. 5; pp. 1234 - 1240
• Main Authors: Michaelson, M.D., Bellmunt, J., Hudes, G.R., Goel, S., Lee, R.J., Kantoff, P.W., Stein, C.A., Lardelli, P., Pardos, I., Kahatt, C., Nieto, A., Cullell-Young, M., Lewis, N.L., Smith, M.R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2012; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Agents, Alkylating - therapeutic use; Biological and medical sciences; chemotherapy; Cohort Studies; Dioxoles - adverse effects; Dioxoles - therapeutic use; docetaxel; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Orchiectomy; Original; Pharmacology. Drug treatments; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Sarcoma - drug therapy; Sarcoma - pathology; Sarcoma - surgery; second-line; Tetrahydroisoquinolines - adverse effects; Tetrahydroisoquinolines - therapeutic use; Trabectedin; Treatment Failure; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; prostate cancer; second-line; docetaxel; chemotherapy; trabectedin; Antineoplastic agent; Human; Urinary system disease; Prostate disease; Multicenter study; Docetaxel; Patient; Malignant tumor; Metastasis; Trabectedin; Resistance; Chemotherapy; Treatment; Castration; Taxane derivatives; Phase II trial; Advanced stage; Antimitotic; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdr399

This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC). 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). 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. Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer.