title: 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.
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-naïve 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.
  
  
  CONCLUSIONS
  This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-naïve CRPC.
authors: Knight Cancer Institute, Oregon Health & Science University, Mail code CH14R, 3303 SW Bond Avenue, Portland, OR 97239, USA. beert@ohsu.edu
authors: T M
authors: TM
authors: Beer
authors: D C
authors: DC
authors: Smith
authors: A
authors: A
authors: Hussain
authors: M
authors: M
authors: Alonso
authors: J
authors: J
authors: Wang
authors: M
authors: M
authors: Giurescu
authors: K
authors: K
authors: Roth
authors: Y
authors: Y
authors: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
chemical_list: D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone; D011241:Prednisone