Hormonal therapy for prostate cancer

Abstract

Updates on hormonal therapy in the treatment of prostate cancer are presented. The most common therapy is to reduce testosterone to castrate levels. A dosage of 1 mg diethylstilbestrol daily prolonged survival in patients with advanced prostate cancer. The leuteinizing hormone-releasing hormone agonists have essentially replaced surgical orchiectomy in the vast majority of clinical settings; however, a major problem with the leuteinizing hormone- releasing hormone agonists has been the surge and flare of testosterone levels. If hormonal therapy is initiated early, the risk of major complications is significantly decreased. Combined androgen blockade is better than monotherapy, although there is only a small clinical benefit. When androgen deprivation is used for a short time and the normal androgen milieu is re-established, the side effects and toxicity of androgen deprivation are decreased. The major complications of androgen deprivation include hot flushes, reduction of bone mineral density, osteoporosis, and anemia. Intermittent androgen blockade might have the same benefits of total androgen suppression with fewer side effects, increased duration of androgen dependence, and less cost. The 10 steps to take when advising patients about initiation of androgen deprivation therapy are reviewed.

Figure 1

Diethylstilbestrol (DES) therapy actuarial survival curves for all causes of death for patients in stages III and IV in study 2. Reprinted, with permission, from Byar and Corle.

Figure 2

Immediate versus deferred treatment for advanced prostate cancer in the Medical Research Council Trial. Data from The Medical Research Council Prostate Cancer Working Party Investigators Group.

Figure 3

Survival advantage of daily flutamide. Note how the curves diverge within just 2–3 months. They then remain parallel for 3.5 years. One wonders whether the “flare” difference in the 2 arms was the cause of the statistically significant difference between the arms. Reprinted from Crawford ED, Eisenberger MA, McLeod DG, et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989;321:419–424. Copyright © 1989 Massachusetts Medical Society. All rights reserved.

Figure 4

Five-year survival curves for 20 trials of androgen suppression plus nilutamide or flutamide versus androgen suppression alone, and 7 trials of androgen suppression plus cyproterone acetate versus androgen suppression alone. Reprinted from The Lancet, volume 355, Maximum androgen blockade in advanced prostate cancer: an overview of the randomized trials. Prostate Cancer Trialists’ Collaborative Group, pp. 1491–1498, copyright 2000, with permission from Elsevier.

Figure 5

Survival benefit with bicalutamide plus castration compared with flutamide plus castration. PCTCG, Prostate Cancer Trialists’ Collaborative Group. Data from references 19 and 20.

Figure 6

Longitudinal effects of aging on date-adjusted testosterone and free testosterone (T) index. Reprinted, with permission, from Harman et al.

Figure 7

Time to first skeletal-related event by treatment in a trial of zoledronate versus placebo. Data from Saad et al.

Figure 8

Time to death by treatment (intent-to-treat patients) in a trial of zoledronate versus placebo. Data from Saad et al.