Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone analogues combined with or without nonsteroidal antiandrogens
is standard treatment for advanced prostate cancer.
The latter is characterized by worsening of symptoms and is caused by the acute increase in serum testosterone concertrations. For example, 3% to 17% of patients receiving an LHRH analog have reported worsening bone pain during the first week of treatment.[25,27,29-32 This flare reaction can be ameliorated by prior and con-current therapy with DES or flutamide (a nonsteroidal antiandrogen), which blocks adrental androgen production.[30,31] It is not know how long flare blockade treatment needs to be administered, but as several deaths have been reported coincident with unblocked flare reactions, use of a blocking agent should be considered.
The nonsteroidal antiandrogen flutamide has been approved for use in combination with LHRH analogs in the treatment of prostate cancer.
The present results are placed in the context of structure-activity knowledge derived from previous modeling studies as well as studies aimed toward designing nonsteroidal antiandrogen pharmaceuticals.
SAR evidence gathered from previous study of an extensive series of nonsteroidal antiandrogens (Tucker et al.
-- A once-daily dosage of the nonsteroidal antiandrogen
bicalutamide decreased the risk of prostate cancer progression by 57%, Dr.
therapy would increase survival by 7.4 years, and diethylstilbestrol would increase survival by 6.9 years.
and luteinizing hormone-releasing hormone (LHRH) analogues are mostly used for metastatic prostate cancer.