Secondary Hormonal Therapies : Prostate
By prostate Doc at 16 September, 2008, 8:28 am
Despite the high initial response to hormonal therapy, virtually all patients with metastatic disease progress. The median time to progression is 16-18 months. When progression occurs, primary androgen deprivation should be maintained.
This approach is supported by a retrospective review of the Eastern Cooperative Oncology Group database showing a superior overall survival for patients maintained on an- drogen deprivation. As discussed above, antiandrogen therapy should be discontin- ued. A number of agents have been tried and have been found to be of limited benefit. Suppression of adrenal androgens with ketoconazole (200-400 mg TID) or aminoglutethimide (1,000-1,750 mg/day) are associated with response rates of ap- proximately 20% and disease stabilization in an additional 30%. Ketoconazole, in particular, has a very rapid onset of action and may be the initial treatment of choice for patients with extreme bone pain or spinal cord compression.
Estrogens and progestins have modest response rates in hormone refractory dis- ease. Estrogens suppress pituitary gonadotropins, resulting in decreased testicular secretion of testosterone. In addition, estrogens have direct cytotoxic effects on tu- mor cells. Diethylstilbestrol, once the mainstay of therapy, is often difficult to ob- tain. Stilphostrol, a parenteral preparation, may be used at a dose of 1-1.5 gm/day for seven days, followed by the same dose, weekly. Other preparations of estrogen have not been well studied in this setting, and it should not be assumed they are equivalent to DES. Progestins act by a mechanism which is unclear. Medroxyprogesterone (500-1,200 mg/day) and megestrol acetate (160-640 mg/day) have similar response rates, ap- proximately 15%. There appears to be no advantage for doses of megestrol acetate higher than 160 mg/day. Other drugs such as tamoxifen, somatostatin analogues, calcitriol, and retinoids have all been studied in the setting of hormone refractory disease. Responses to the first two have been observed in approximately 20% of patients, while there have been no clear responses to either calcitriol or all-trans-retinoic acid as single agents. Other retinoids are currently being studied.
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