Hormone/antihormone withdrawal and dexamethasone for hormone-refractory prostate cancer

Flutamide withdrawal has been reported to benefit patients with hormone-refractory prostate cancer. Several studies have also demonstrated that a combination of corticosteroids and testicular androgen ablation lowers serum androgen levels and improves clinical response. The purpose of this study was to examine the effect of withdrawal of oral hormonal agents and administration of dexamethasone in stage D3 prostate cancer patients.

Sixteen patients with hormone-refractory prostate cancer were enrolled in the study. All patients had osseous metastasis and elevated serum prostate-specific antigen. Nine had been treated with chlormadinone acetate, 4 with estramustine phosphate, and 3 with flutamide as first-line hormonal therapy. All patients had also been treated either with bilateral orchiectomy (13 cases) or a luteinizing hormone-releasing hormone (LH-RH) agonist (3 cases). Seven patients whose disease progressed following hormone withdrawal were treated with oral dexamethasone (initially 1.5 mg/day, then tapered to 0.5 mg/day).

Eight patients demonstrated a decrease in prostate-specific antigen of greater than 50% following hormone withdrawal. The time to cancer progression for these 8 patients was 2 to 15 months (mean, 4 months). Among the patients receiving dexamethasone, 4 showed a greater than 90% decrease in prostate-specific antigen after 3 months' treatment. The time to disease progression for these 4 patients was 3 to 11 months.

In treating hormone-refractory advanced prostate cancer, the first pharmacologic manipulation should be withdrawal of the oral component of combined hormonal therapy. Patients whose disease progresses after hormone withdrawal should then be treated with glucocorticoids such as dexamethasone.