title: Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival.
  
  
  METHODS
  The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks.
  
  
  RESULTS
  Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue.
  
  
  CONCLUSIONS
  Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jeanny B
authors.initials: JB
authors.lastname: Aragon-Ching
authors.forename: Lokesh
authors.initials: L
authors.lastname: Jain
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: David
authors.initials: D
authors.lastname: Draper
authors.forename: Jürgen
authors.initials: J
authors.lastname: Venitz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jones
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D009919:Orchiectomy; D010671:Phenylurea Compounds; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000077157:Sorafenib; D016896:Treatment Outcome; D048490:raf Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D007987:Gonadotropin-Releasing Hormone; D000077157:Sorafenib; D048490:raf Kinases