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Prolonged response to flutamide withdrawal and initiation of aminoglutethimide in a patient with metastatic prostate cancer

Clinical Pharmacokinetics Section, Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Richard M. Lush, PhD

Clinical Pharmacokinetics Section, Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Oliver Sartor, MD

Clinical Pharmacokinetics Section, Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Eddie Reed, MD

Clinical Pharmacokinetics Section, Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

William D. Figg, PharmD

Clinical Pharmacokinetics Section, Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Objective. To present a patient with metastatic pros tate cancer who has experienced an extended re sponse to the withdrawal of flutamide and the con comitant initiation of aminoglutethimide.

Case Summary. A 73-year-old male was diagnosed with advanced metastatic prostate cancer. He received treatment with suramin, leuprolide, and flutamide. After progressing on this regimen his flutamide was discon tinued and aminoglutethimide was initiated. His re sponse to this treatment has reached almost 3 years, with no evidence of progression.

Discussion. The response to the withdrawal of flutamide is thought to arise from a mutated androgen receptor that recognizes hydroxyflutamide, the active metabolites of flutamide, as an agonist. The receptor continues to recognize endogenous steroids as agonists. The addition of the adrenal steroid synthesis inhibitor, aminoglutethimide may play a role in enhancing this response phenomenon.

Conclusions. This patient is progression free for approximately 3 years following the withdrawal of flutamide. This maneuver has been found to have activity in a subset of patients who have been treated for metastatic prostate cancer with combined andro gen blockade.

Key Words: Prostate cancer • flutamide withdrawal • hormonal therapy.

Journal of Oncology Pharmacy Practice, Vol. 1, No. 3, 45-47 (1995)
DOI: 10.1177/107815529500100309


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