Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer.
OBJECTIVE
Casodex (Zeneca) is a new potent, long-acting non-steroidal anti-androgen, which produces androgen deprivation by blocking the androgen receptor. We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer.


METHODS
As part of a large, multicentre study comparing the therapeutic effects of surgical castration with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a subgroup of 23 patients on Casodex were studied in detail for changes in endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol, prolactin, sex hormone binding globulin and free testosterone were measured at the start of therapy and after 1, 4, 8, 12 and 24 weeks. Effects on libido, sexual activity and the appearance of hot flushes, breast pain and gynaecomastia were recorded.


RESULTS
Administration of Casodex resulted in a rise in LH levels in all patients with a mean increase after 24 weeks of 102% (P < 0.001). Mean FSH levels showed a limited increase (7%) after 24 weeks, which was significant only after 1 week (P < 0.001). As a result of the high LH levels, total testosterone levels increased after 24 weeks by 66% (P < 0.001), free testosterone by 57% (P < 0.001) and dihydrotestosterone by 24% (P = 0.0112). Parallel to testosterone, oestradiol levels rose by a mean of 66% (P < 0.001). Mean sex hormone binding globulin and prolactin levels rose by respectively 8% (P = NS) and 65% (P < 0.01). Despite an increase in testosterone levels, excellent androgen blockade was obtained, as shown by a decrease in prostate specific antigen levels in 22/23 patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No patient complained of hot flushes. However, mild gynaecomastia and/or breast tenderness were seen in 48 and 30% of cases respectively.


CONCLUSIONS
Casodex 150 mg/day monotherapy resembles surgical castration in achieving androgen deprivation, despite an increase in LH and testosterone levels. In contrast to castration, libido and sexual activity are usually maintained and hot flushes are rare. However, mild gynaecomastia and/or breast tenderness were noted in 48 and 30% of patients.
Verhelst
J
J
Department of Endocrinology, A. Z. Middleheim, Antwerp, Belgium.
Denis
L
L
Van Vliet
P
P
Van Poppel
H
H
Braeckman
J
J
Van Cangh
P
P
Mattelaer
J
J
D'Hulster
D
D
Mahler
C
C
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009919:Orchiectomy; D011388:Prolactin / Q000097:blood*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D012739:Gonadal Steroid Hormones; D006065:Gonadotropins, Pituitary; D009570:Nitriles; D014105:Tosyl Compounds; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C053541:bicalutamide; D017430:Prostate-Specific Antigen