title: A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer.
abstract: OBJECTIVE
  The objective of this trial was to evaluate the clinical effects of sorafenib, a multi-targeted kinase inhibitor, in combination with androgen receptor blockade in patients with castration-resistant prostate cancer.
  
  
  METHODS
  This was a multicenter, two-stage, phase 2 trial. Eligible patients had rising PSA, minimal symptoms and were chemotherapy-naïve. Sorafenib 400 mg twice daily was administered with bicalutamide 50 mg once daily on a 28-day cycle. The primary endpoint was PSA response (≥ 50% decline) or stable disease ≥ 6 months.
  
  
  RESULTS
  39 patients were enrolled including eight without clinical evidence of metastases. Eighteen (47%) patients have had either a PSA response or stable disease ≥ 6 months. PSA declines of ≥ 50% occurred in 12 (32%) of 38 assessable patients, including seven of 27 patients (26%) with prior anti-androgen use. Median time to treatment failure was 5.5 months (95%CI = 4.8.1-8.3). Grade ≥ 3 adverse events included fatigue, skin rash, and hand-foot syndrome.
  
  
  CONCLUSIONS
  PSA declines and stable disease were observed with a combination of sorafenib and bicalutamide including in patients previously progressing on bicalutamide. Strategies to combine multi-targeted kinase inhibitors with hormonal therapies warrant further study in patients with CRPC.
authors.affiliation: BC Cancer Agency - Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Beardsley
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ellard
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D009919:Orchiectomy; D010671:Phenylurea Compounds; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D013997:Time Factors; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D009570:Nitriles; D010671:Phenylurea Compounds; D011725:Pyridines; D014105:Tosyl Compounds; D009536:Niacinamide; D000077157:Sorafenib; C053541:bicalutamide; D017430:Prostate-Specific Antigen