Surprising activity of nilutamide in post-castration progressive prostate cancer

Abstract

4762 Background: Increasingly patients with post-castration prostate cancer seek treatment for PSA only progression. Many of these patients are elderly, have considerable co-morbidities, are concerned about a rising PSA, and seek relatively non-toxic therapies. Methods: Twelve patients with progressive post-castration prostate cancer were treated with oral nilutamide at FDA approved doses (150 mg/day). LHRH agonist maintenance therapy was continued in non-surgically castrated patients. Monthly PSA monitoring was recommended. PSA progression was defined as a 25% increase from baseline or nadir with a minimum increase of 5 ng/ml as recommended by Bubley et al (J Clin Oncol 17:3461). Results: All patients had failed either orchiectomy (n=2) or LHRH agonist therapy (n=10) and had clear evidence of a rising PSA prior to starting nilutamide. Median age was 81 (range 62–87), median PSA was 12 ng/ml (range 2.7–92.1), and radiographically positive metastatic disease was present in 33% (4/12). Antiandrogens were previously used in 50% of patients (5/12 were bicalutamide pretreated, 1/12 were pretreated with flutamide). PSA declines were noted in 9/12 patients; PSA declines of >50% were noted in 4/12 (33%) patients. Median progression free survival was 7 months (range 1–36+). One patient had CT evidence of progression without PSA progression. Progression-free survival of more than 6 months was noted in both antiandrogen (4/6) and non-antiandrogen (2/6) pretreated patients. One patient became nauseated after four doses and refused further therapy, two patients had fatigue and weight loss and stopped therapy prior to PSA progression. No other toxicities were noted except alterations in visual light-dark adaptation Conclusions: Nilutamide at FDA approved dosages can delay PSA progression in patients with prostate cancer failing to respond to primary androgen deprivation therapies. Toxicities necessitated cessation of therapy in 3/12 patients. No significant financial relationships to disclose.