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Research Articles |
Authors' Affiliations: 1 Medical Oncology Unit, 2 Urology Unit, 3 Pathology Unit, and 4 Clinical Chemistry and Microbiology Laboratory, Galliera Hospital; 5 Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy; 6 Section of Pathological Anatomy, Polytechnic University of the Marche Region, Ancona, Italy; and 7 Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy
Requests for reprints: Andrea Decensi, Medical Oncology Unit, Galliera Hospital, Mura delle Cappuccine 14, 16128 Genova, Italy. Phone: 39-010-5634501; Fax: 39-010-57481090; E-mail: andrea.decensi{at}galliera.it.
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.
Key Words: Chemoprevention • Prostate cancer • Bicalutamide • High-grade prostatic intraepithelial neoplasia • Circulating biomarkers
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