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

M. D. Michaelson, J. Bellmunt, G. R. Hudes, Sanjay Goel, R. J. Lee, P. W. Kantoff, C. A. Stein, P. Lardelli, I. Pardos, C. Kahatt, A. Nieto, M. Cullell-Young, N. L. Lewis, M. R. Smith

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Abstract

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/m 2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m 2 (Cohort B1, n = 5) and 1.2 mg/m 2 (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/m. 2 (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m. 2 q3wk and 0.58 mg/m. 2 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.

Original languageEnglish (US)
Pages (from-to)1234-1240
Number of pages7
JournalAnnals of Oncology
Volume23
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

trabectedin
Castration
Prostate-Specific Antigen
Prostatic Neoplasms
Appointments and Schedules
Safety
Transaminases
Neutropenia
Sarcoma
Nausea
Fatigue
Drug Therapy

Keywords

  • Chemotherapy
  • Docetaxel
  • Prostate cancer
  • Second-line
  • Trabectedin

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Michaelson, M. D., Bellmunt, J., Hudes, G. R., Goel, S., Lee, R. J., Kantoff, P. W., ... Smith, M. R. (2012). Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer. Annals of Oncology, 23(5), 1234-1240. https://doi.org/10.1093/annonc/mdr399

Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer. / Michaelson, M. D.; Bellmunt, J.; Hudes, G. R.; Goel, Sanjay; 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.

In: Annals of Oncology, Vol. 23, No. 5, 05.2012, p. 1234-1240.

Research output: Contribution to journalArticle

Michaelson, MD, Bellmunt, J, Hudes, GR, Goel, S, Lee, RJ, Kantoff, PW, Stein, CA, Lardelli, P, Pardos, I, Kahatt, C, Nieto, A, Cullell-Young, M, Lewis, NL & Smith, MR 2012, 'Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer', Annals of Oncology, vol. 23, no. 5, pp. 1234-1240. https://doi.org/10.1093/annonc/mdr399
Michaelson, M. D. ; Bellmunt, J. ; Hudes, G. R. ; Goel, Sanjay ; 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. / Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer. In: Annals of Oncology. 2012 ; Vol. 23, No. 5. pp. 1234-1240.
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abstract = "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/m 2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m 2 (Cohort B1, n = 5) and 1.2 mg/m 2 (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/m. 2 (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m. 2 q3wk and 0.58 mg/m. 2 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.",
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AU - Bellmunt, J.

AU - Hudes, G. R.

AU - Goel, Sanjay

AU - Lee, R. J.

AU - Kantoff, P. W.

AU - Stein, C. A.

AU - Lardelli, P.

AU - Pardos, I.

AU - Kahatt, C.

AU - Nieto, A.

AU - Cullell-Young, M.

AU - Lewis, N. L.

AU - Smith, M. R.

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N2 - 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/m 2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m 2 (Cohort B1, n = 5) and 1.2 mg/m 2 (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/m. 2 (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m. 2 q3wk and 0.58 mg/m. 2 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.

AB - 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/m 2 for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m 2 (Cohort B1, n = 5) and 1.2 mg/m 2 (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/m. 2 (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m. 2 q3wk and 0.58 mg/m. 2 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.

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