title: A phase II study of nilutamide in men with prostate cancer after the failure of flutamide or bicalutamide therapy.
abstract: OBJECTIVE
  To determine the prostate-specific antigen (PSA) response and time to PSA or radiographic progression in men with prostate cancer refractory to bicalutamide and/or flutamide therapy.
  
  
  METHODS
  Men with histologically confirmed prostate cancer not amenable to curative surgery or radiation therapy were eligible for the study if they had radiographic or PSA progression on at least one antiandrogen (not nilutamide) despite continued androgen suppression and standard antiandrogen withdrawal periods. All men received nilutamide 150 mg/day orally for > or = 8 weeks unless there was unacceptable toxicity or disease progression. All men were evaluated for response, safety and toxicity. Baseline PSA levels, chest X-ray, bone scan and abdominopelvic computed tomography studies were obtained; the re-evaluation included PSA levels every 4 weeks and repeated imaging every 8 weeks in those with baseline abnormalities. The chest X-ray was repeated if there were pulmonary symptoms. Nineteen men were consented and 16 were evaluable for response.
  
  
  RESULTS
  The median (range) Gleason score was 7 (6-9) and the median number of previous second-line therapies was 2 (1-4). Bicalutamide therapy had failed in all patients. At baseline, 13 (of 16 men) had radiographically evident disease, nine with diffuse osseous and four with radiographically measurable metastases. There was no grade 3/4 toxicity; the commonest grade 1/2 toxicities were constipation (three), sensory neuropathy (four), fatigue (six), and visual changes (two) involving transiently altered colour vision and sensitivity to light, respectively. Responses included three partial and 13 with progressive disease.
  
  
  CONCLUSIONS
  The study was discontinued after a planned interim analysis because nilutamide had no apparent activity. Although well tolerated, nilutamide offers benefit to few men with prostate cancer in whom bicalutamide has failed.
authors.affiliation: Division of Neoplastic Diseases and Related Disorders, Medical College of Wisconsin, Milwaukee, WI, USA. ndavis@mcw.edu
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Davis
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018450:Disease Progression; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D048289:Imidazolidines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D014105:Tosyl Compounds; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D048289:Imidazolidines; D009570:Nitriles; D014105:Tosyl Compounds; C021277:nilutamide; D005485:Flutamide; C053541:bicalutamide; D017430:Prostate-Specific Antigen