title: Phase I-II trial of weekly bicalutamide in men with elevated prostate-specific antigen and negative prostate biopsies.
abstract: BACKGROUND
  Men with elevated prostate-specific antigen (PSA) and negative prostate biopsies are at risk for prostate cancer. The antiandrogen bicalutamide has a prolonged half-life, thus potentially allowing an intermittent administration to retain activity while reducing toxicity. We conducted a phase I-II trial of weekly bicalutamide in men with PSA >4 ng/mL and negative biopsies.
  
  
  METHODS
  Eighty subjects were nonrandomly assigned to a three-arm trial to either bicalutamide 50 mg/wk (n = 26) or 100 mg/wk (n = 28) or no treatment (n = 26) for 6 months. Blood samples were obtained at 0, 3, and 6 months, and prostate biopsies were repeated after 6 months. The outcome measures were 6-month changes of tissue Ki-67 (primary end point), high-grade prostatic intraepithelial neoplasia (HG-PIN), proliferative inflammatory atrophy, circulating PSA, and sex hormones.
  
  
  RESULTS
  Ki-67 expression was higher in HG-PIN than in normal tissue (10% versus 3%; P < 0.01) but was not modulated by bicalutamide in normal luminal cells. A trend toward an improvement of HG-PIN status was found in treated subjects (26% improved, 60% had no change, 15% worsened) as compared with the no-treatment arm (4% improved, 83% had no change, 13% worsened; P = 0.07). Proliferative inflammatory atrophy prevalence was not reduced by bicalutamide. Bicalutamide reduced PSA by 50% in both arms and raised testosterone and estradiol levels. Asymptomatic breast swelling was noted in 40% of the treated cases.
  
  
  CONCLUSIONS
  A weekly administration of bicalutamide seems to be reasonably safe and shows an encouraging signal of activity on HG-PIN prevalence, supporting further studies of this schedule in men at high risk despite the negative primary end-point findings on Ki-67.
authors.affiliation: Medical Oncology Unit, Galliera Hospital, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanardi
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffezzini
authors.forename: Roberto
authors.initials: R
authors.lastname: Bandelloni
authors.forename: Marco
authors.initials: M
authors.lastname: Mori
authors.forename: Alessandra
authors.initials: A
authors.lastname: Argusti
authors.forename: Fabio
authors.initials: F
authors.lastname: Campodonico
authors.forename: Laura
authors.initials: L
authors.lastname: Turbino
authors.forename: Daniela
authors.initials: D
authors.lastname: Branchi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Andrea
authors.initials: A
authors.lastname: Decensi