Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: A phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium

T. M. Beer, D. C. Smith, A. Hussain, M. Alonso, J. Wang, M. Giurescu, K. Roth, Y. Wang

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17 Citations (Scopus)

Abstract

Background:Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC).Methods:Chemotherapy- nave patients with metastatic CRPC received sagopilone (one cycle: 16 mg m -2 intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (≥50% PSA reduction confirmed ≥28 days apart). According to the Simon two-stage design, ≥3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available.Results:In all, 53 patients received ≥2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m-2 during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity.Conclusion: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-nave CRPC.

Original languageEnglish (US)
Pages (from-to)808-813
Number of pages6
JournalBritish journal of cancer
Volume107
Issue number5
DOIs
StatePublished - Aug 21 2012

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Castration
Prednisone
Prostatic Neoplasms
Clinical Trials
Prostate-Specific Antigen
Epothilones
Drug Therapy
Peripheral Nervous System Diseases
Patient Selection
Compliance
Disease-Free Survival
Fatigue
sagopilone
Neoplasms
Extremities
Safety
Pain

Keywords

  • clinical trial
  • epothilones
  • phase II
  • prednisone
  • prostatic neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer : A phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium. / Beer, T. M.; Smith, D. C.; Hussain, A.; Alonso, M.; Wang, J.; Giurescu, M.; Roth, K.; Wang, Y.

In: British journal of cancer, Vol. 107, No. 5, 21.08.2012, p. 808-813.

Research output: Contribution to journalArticle

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abstract = "Background:Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC).Methods:Chemotherapy- nave patients with metastatic CRPC received sagopilone (one cycle: 16 mg m -2 intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (≥50{\%} PSA reduction confirmed ≥28 days apart). According to the Simon two-stage design, ≥3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available.Results:In all, 53 patients received ≥2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m-2 during initial six cycles, mean dose intensity 94±9{\%}. The confirmed PSA response rate was 37{\%}. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10{\%} of patients) were peripheral neuropathy (94.3{\%}), fatigue (54.7{\%}) and pain in the extremities (47.2{\%}). Sagopilone was associated with very little haematological toxicity.Conclusion: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-nave CRPC.",
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AB - Background:Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC).Methods:Chemotherapy- nave patients with metastatic CRPC received sagopilone (one cycle: 16 mg m -2 intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (≥50% PSA reduction confirmed ≥28 days apart). According to the Simon two-stage design, ≥3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available.Results:In all, 53 patients received ≥2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m-2 during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity.Conclusion: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-nave CRPC.

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