Adrenal androgen levels as predictors of outcome in castration-resistant prostate cancer patients treated with combined androgen blockade using flutamide as a second-line anti-androgen.
OBJECTIVE
To analyze the clinical effects of flutamide as a second-line anti-androgen for combined androgen blockade in patients with castration-resistant prostate cancer (CRPC) initially treated with bicalutamide as a first-line anti-androgen.


METHODS
Our study population consisted of 16 patients with CRPC who were treated with flutamide (375 mg daily) as second-line hormonal therapy. Dehydroepiandrosterone (DHEA), androstenedione, androstenediol, testosterone and dihydrotestosterone were measured to investigate the relationship between plasma androgens and outcome following treatment. Furthermore, adrenal androgen levels in a medium of adrenal cancer cell line were also measured.


RESULTS
Second-line hormonal therapy using flutamide resulted in a reduction of the prostate-specific antigen (PSA) level in 14 (87.5%) of 16 patients. A PSA decline greater than 50% was observed in 8 (50%) of the 16 patients. The duration of median responsiveness was 6.25 months. PSA elevation of baseline androstenediol level was a predictive factor of PSA responsiveness. The lower DHEA group improved the duration of responsiveness to flutamide. In vitro, 3 micromol/L flutamide suppressed DHEA, androstenedione and androstenediol synthesis compared with bicalutamide in a medium of adrenal cancer cell line.


CONCLUSIONS
Our data show that flutamide suppresses the adrenal androgens in comparison with bicalutamide. The responsiveness and response duration of flutamide can be predicted in patients with a higher baseline androstenediol level and a lower DHEA level. Metabolites from adrenal androgens contribute to the progression of prostate cancer.
Narimoto
Kazutaka
K
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Mizokami
Atsushi
A
Izumi
Kouji
K
Mihara
Shinya
S
Sawada
Kiyoshi
K
Sugata
Toshiaki
T
Shimamura
Masayoshi
M
Miyazaki
Kimiomi
K
Nishino
Akio
A
Namiki
Mikio
M
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000311:Adrenal Glands / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000097:blood* / Q000378:metabolism; D045744:Cell Line, Tumor; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016879:Salvage Therapy
D000726:Androgen Antagonists; D000728:Androgens; D005485:Flutamide; D017430:Prostate-Specific Antigen