Response to cyproterone acetate treatment in primary hepatocellular carcinoma is related to fall in free 5 alpha-dihydrotestosterone.
The male preponderance in cirrhotic patients with primary hepatocellular carcinoma (HCC) and the presence of androgen receptors in tumour tissue suggest possible benefit from anti-androgenic therapy. Twenty-five cirrhotic patients with irresectable HCC (23 male) were treated with cyproterone acetate (CPA) 300 mg daily. Hepatic ultrasound, alpha-fetoprotein and total and free sex steroid levels were monitored. Five patients had an objective response to therapy with a median duration of 8 weeks and survival in excess of 29 weeks. Median survival for all patients was 14 weeks. Apart from transient paranoia in two cases, side-effects were minimal. Total androgen levels (measured in 13 patients) had fallen significantly at 10 weeks, but free 5 alpha-dihydrotestosterone (DHT) which had fallen by 4.8 pM (median) in five responders, had risen by 5.05 pM in eight non-responders: P less than 0.025. The apparent correlation of response with reduction in free DHT suggests that hormonal manipulation may be effective in HCC if free DHT is reliably reduced. This has been achieved in other conditions by the combination of CPA with low dose oestrogen or with LHRH agonists.
Forbes
A
A
Liver Unit, King's College School of Medicine and Dentistry, Denmark Hill, London, U.K.
Wilkinson
M L
ML
Iqbal
M J
MJ
Johnson
P J
PJ
Williams
R
R
D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017373:Cyproterone Acetate; D013196:Dihydrotestosterone / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy*
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D012739:Gonadal Steroid Hormones; D013196:Dihydrotestosterone; D017373:Cyproterone Acetate; D003534:Cyproterone