Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma

Background. Men with prostate carcinoma initially respond to therapies desi gned to inhibit androgen secretion or block its action. Later, the tumors i n these patients become refractory to androgen-related therapies. Therefore , additional hormonal maneuvers that would benefit these men currently are needed. Reports of androgen receptor mutations and historic clinical observ ations raised the hypothesis that estrogens might be involved in the prolif eration of androgen-refractory prostate carcinoma. Methods. To explore this hypothesis, 14 men with advanced prostate carcinom a that was refractory to medical or surgical orchiectomy and antiandrogens were entered into a clinical Phase II trial involving suppression of estrog ens. After complete evaluation, each patient received 1 mg daily of the thi rd-generation aromatase inhibitor anastrozole until disease progression. Fo llow-up included serial determinations of prostate specific antigen (PSA), measurements of evaluable lesions, and assessment of intensity of pain. Results. No patient experienced an objective response or disease stabilizat ion as measured by PSA level or the greatest dimension of the lesion. Minim al improvement of bone pain was reported in two patients receiving intensiv e analgesic medication. Conclusions. It was concluded that the dependence of androgen-insensitive p rostate carcinoma on estrogens for proliferation is uncommon and that aroma tase inhibitors may not have a place in the treatment of prostate carcinoma at this stage of the disease. Cancer 2001;92:2095-101. (C) 2001 American C ancer Society.