Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma.

BACKGROUND

Although antiandrogen withdrawal has moderate efficacy in patients with hormone refractory prostate carcinoma (HRPC), the effect of the simultaneous suppression of adrenal androgens with ketoconazole at the time of antiandrogen withdrawal is not known.

METHODS

Twenty consecutive patients with HRPC who had developed progressive disease despite combined androgen blockade were treated with antiandrogen withdrawal and simultaneous ketoconazole as a means of inhibiting adrenal steroid production. Prostate specific antigen (PSA) response was defined as a > 50% fall in PSA from baseline that was maintained for at least 8 weeks.

RESULTS

Ten patients had established metastatic disease, 2 had high PSAs and no imaging studies (PSA of 70 and 160 ng/mL, respectively), 3 had microscopically positive lymph nodes and serologic progression, and 5 had serologic progression alone. Overall, of 20 evaluable patients, 11 (55%) had a > 50% fall in PSA (95% confidence interval [CI], 31.5-76.9%). The median PSA response duration was 8.5 months (95% CI, 7-17 months). The median survival was 19 months. Toxicity was mild, with Grade 1 and 2 nausea and emesis in 15% of patients, Grade 1 fatigue in 10% of patients, and reversible Grade 1 or 2 hepatotoxicity in 10% of patients. Mild skin toxicity was observed in 20% of patients.

CONCLUSIONS

The addition of ketoconazole and hydrocortisone to antiandrogen withdrawal appears to increase the PSA response proportion observed with antiandrogen withdrawal alone. Toxicity is mild.