Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade.
OBJECTIVE
Large meta-analyses have documented that maximum androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer confers survival benefits, although it remains controversial. Also, we and others have reported the effectiveness of second line hormonal therapy for prostate cancer that relapses after initial hormone therapy. However, there is little clinical evidence of the effectiveness of the latter treatment strategy. Therefore, in this multicenter trial in Japan we analyzed clinical outcomes following alternative changing from 1 nonsteroidal antiandrogen to another, ie bicalutamide to flutamide and flutamide to bicalutamide, for advanced prostate cancer that relapsed after initial maximum androgen blockade.


METHODS
The study included 232 patients with advanced prostate cancer who were initially treated with maximum androgen blockade, including surgical or medical castration combined with nonsteroidal antiandrogens. If a patient relapsed while on first line therapy, we discontinued antiandrogen and evaluated the patient for antiandrogen withdrawal syndrome. We then administered an alternative antiandrogen and evaluated its effect.


RESULTS
The incidence of antiandrogen withdrawal syndrome after initial maximum androgen blockade was 15.5% for bicalutamide and 12.8% for flutamide. A prostate specific antigen decrease after antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as alternative therapy in patients with relapse after the initial maximum androgen blockade were effective (prostate specific antigen decrease greater than 50%) as second line maximum androgen blockade. Of 232 patients 142 (61.2%) showed a prostate specific antigen decrease in response to an alternative antiandrogen. These responders had significantly better survival than nonresponders, suggesting that responsiveness to second line therapy predicts increased survival.


CONCLUSIONS
Following maximum androgen blockade with an alternative nonsteroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial maximum androgen blockade. Even a partial response to second line maximum androgen blockade was associated with improved survival. Our data support the notion that responders to second line regimens are androgen independent but still hormonally sensitive.
Suzuki
Hiroyoshi
H
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan. hirosuzu@faculty.chiba-u.jp
Okihara
Koji
K
Miyake
Hideaki
H
Fujisawa
Masato
M
Miyoshi
Susumu
S
Matsumoto
Tetsuro
T
Fujii
Motohiro
M
Takihana
Yoshio
Y
Usui
Tsuguru
T
Matsuda
Tadashi
T
Ozono
Seiichiro
S
Kumon
Hiromi
H
Ichikawa
Tomohiko
T
Miki
Tsuneharu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome; D016019:Survival Analysis; D014105:Tosyl Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide; D017430:Prostate-Specific Antigen