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Clinical and biochemical effect of aminoglutethimide in the treatment of advanced prostatic carcinoma
Abstract:
Treatment of male patients with advanced prostatic carcinoma and disease progression after initial endocrine therapy frequently is unsatisfactory. However, approximately 20 per cent of these patients respond to surgical adrenalectomy or hypophysectomy, indicating continued hormonal responsiveness. A total of 25 previously castrated men with stage D carcinoma received 1,000 mg. aminoglutethimide and 40 mg. hydrocortisone daily. The patients were evaluated using the criteria of the National Prostatic Cancer Project. One patient has had a complete response and is in remission after 275 weeks of therapy. A partial response was noted in 4 patients, while the disease was objectively stable in 6. Pre-treatment testosterone and dihydrotestosterone levels were measured in 9 of 25 patients and were significantly reduced statistically during aminoglutethimide therapy (p less than 0.01). Response and drug toxicity are discussed.
Insights
Aminoglutethimide and hydrocortisone treatment showed efficacy in some advanced prostate cancer patients resistant to initial endocrine therapy. This combination therapy reduced testosterone levels and demonstrated objective responses in a subset of patients.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Advanced prostatic carcinoma often shows disease progression despite initial endocrine therapy, necessitating alternative treatment strategies.
- Surgical adrenalectomy or hypophysectomy can induce responses in approximately 20% of these patients, suggesting continued hormonal dependence.
Observation:
- A study involved 25 previously castrated men with stage D carcinoma receiving 1,000 mg aminoglutethimide and 40 mg hydrocortisone daily.
- Patient responses were evaluated using National Prostatic Cancer Project criteria.
Findings:
- One patient achieved a complete response and remission lasting over 275 weeks.
- Four patients showed a partial response, and six had objectively stable disease.
- Aminoglutethimide therapy significantly reduced pre-treatment testosterone and dihydrotestosterone levels (p < 0.01).
Implications:
- Aminoglutethimide, in combination with hydrocortisone, represents a potential therapeutic option for hormone-refractory advanced prostate cancer.
- The observed reduction in androgen levels supports the hormonal mechanism of action.
- Further investigation into drug toxicity and patient selection is warranted.