Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma.
BACKGROUND
Men with prostate carcinoma initially respond to therapies designed to inhibit androgen secretion or block its action. Later, the tumors in 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 observations raised the hypothesis that estrogens might be involved in the proliferation of androgen-refractory prostate carcinoma.


METHODS
To explore this hypothesis, 14 men with advanced prostate carcinoma that was refractory to medical or surgical orchiectomy and antiandrogens were entered into a clinical Phase II trial involving suppression of estrogens. After complete evaluation, each patient received 1 mg daily of the third-generation aromatase inhibitor anastrozole until disease progression. Follow-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 stabilization as measured by PSA level or the greatest dimension of the lesion. Minimal improvement of bone pain was reported in two patients receiving intensive analgesic medication.


CONCLUSIONS
It was concluded that the dependence of androgen-insensitive prostate carcinoma on estrogens for proliferation is uncommon and that aromatase inhibitors may not have a place in the treatment of prostate carcinoma at this stage of the disease.
Santen
R J
RJ
Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA. rjs5y@virginia.edu
Petroni
G R
GR
Fisch
M J
MJ
Myers
C E
CE
Theodorescu
D
D
Cohen
R B
RB
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010147:Pain Measurement; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D017430:Prostate-Specific Antigen