title: Antiandrogen-associated hepatotoxicity in the management of advanced prostate cancer.
abstract: BACKGROUND
  Antiandrogens available for patients with advanced prostate cancer are reported to cause hepatotoxicity. The aim of this study is to investigate the antiandrogen-associated hepatotoxicity in patients with advanced prostate cancer.
  
  
  METHODS
  By retrospective charts review, 229 patients (47-89 years old) with advanced prostate cancer treated by total androgen blockade (TAB) with bilateral orchiectomy or LHRH (luteinizing hormone-releasing hormone) analogues plus antiandrogen, or antiandrogen-radiotherapy were enrolled in this study. There were 124 patients taking flutamide 750 mg daily and 105 patients taking cyproterone acetate (CPA) 150 mg daily. Hepatotoxicity defined by the International Consensus Meeting in 1990 and Food and Drug Administration, USA was used to evaluate the hepatotoxicity (including serious hepatotoxicity).
  
  
  RESULTS
  There was a higher occurrence of hepatotoxicity in patients taking flutamide (15.3%) than taking CPA (9.5%) (p = 0.034). The occurrence of serious hepatotoxicity of flutamide and CPA was 4.8% (6/124) and 3.8% (4/105), respectively. The mean latency period of hepatotoxicity for CPA was 4.8 +/- 2.0 months for flutamide and 5.8 +/- 1.9 months for CPA, respectively. The 2 groups made no significant difference of liver enzyme (mean maximal alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) = 284.2 +/- 99.3/300.6 +/- 58.5 U/L versus 341.8 +/- 67.1/301.6 +/- 80.5 U/L). All of the 19 patients (100%) and 9 of 10 patients (90%) with flutamide and CPA-induced hepatotoxicity got self-resolution after discontinuation of the antiandrogens. The average time of self-resolution is 4.5 +/- 3.1 months and 6.3 +/- 4.7 months for flutamide and CPA, respectively. Five patients of flutamide-induced and 2 patients of CPA-induced hepatotoxicity got resolution after changing to other antiandrogen.
  
  
  CONCLUSIONS
  Flutamide and CPA appear to cause hepatotoxic effects in some patients. Discontinuation of the antiandrogens seems to be the resolution of hepatotoxicity. A change to other antiandrogen may be the alternative strategy to the antiandrogen-induced hepatotoxicity. The results of this study suggest that all patients received flutamide and CPA should be monitored carefully for signs and symptoms referable to hepatic injury to prevent the development of serious hepatic dysfunction.
authors.affiliation: Division of Urology, Department of Surgery, Taipei Veterans General Hospital, Taiwan, ROC.
authors.forename: Alpha D Y
authors.initials: AD
authors.lastname: Lin
authors.forename: Kuang-Kuo
authors.initials: KK
authors.lastname: Chen
authors.forename: Alex T L
authors.initials: AT
authors.lastname: Lin
authors.forename: Yen-Hwa
authors.initials: YH
authors.lastname: Chang
authors.forename: Howard H H
authors.initials: HH
authors.lastname: Wu
authors.forename: Junne-Yih
authors.initials: JY
authors.lastname: Kuo
authors.forename: William J S
authors.initials: WJ
authors.lastname: Huang
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Hsu
authors.forename: Hsiao-Jen
authors.initials: HJ
authors.lastname: Chung
authors.forename: Luke S
authors.initials: LS
authors.lastname: Chang
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D017373:Cyproterone Acetate / Q000009:adverse effects*; D005485:Flutamide / Q000009:adverse effects*; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000628:therapy; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D017373:Cyproterone Acetate; D005485:Flutamide