Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy.
OBJECTIVE
We studied the efficiency of second or third line hormonal therapy for prostate cancer relapse after hormone therapy.


METHODS
The study included 70 patients with advanced prostate cancer treated with hormonal therapy, androgen deprivation monotherapy or maximum androgen blockade including surgical or medical castration combined with steroidal antiandrogen, 100 mg chlormadinone acetate daily or nonsteroidal antiandrogens, 375 mg flutamide (FLT) daily or 80 mg bicalutamide (BCL) daily. When the disease relapsed, we discontinued the antiandrogen and evaluated the patient for the antiandrogen withdrawal syndrome (AWS). Thereafter we administrated an alternative antiandrogen and evaluated its effect.


RESULTS
The incidence of the AWS after first, second and third line hormonal therapy was 35.8%, 8.0% and 0%, respectively. The efficiency of subsequent hormonal therapy was not related to the occurrence of the AWS. Nonsteroidal antiandrogens as alternative therapies for disease relapse from primary therapy were effective in second line (FLT 38.1%, BCL 44.4%) or in third line (FLT 30.0%, BCL 28.6%) hormonal therapy. Of 5 (80%) patients who responded to second line therapy 4 (80%) had effective third line therapy, while only 1 of 12 (8.3%) second line nonresponders had effective third line therapy (p = 0.003). The survival of second line responders was significantly better than that of nonresponders (5-year survival rate 92.3% vs 23.9%, p <0.001), indicating a potential predictive value for second line responsiveness. No significant clinical factor identified second line responsiveness.


CONCLUSIONS
Subsequent nonsteroidal antiandrogen therapies were effective against prostate cancer relapse after hormonal therapy. The response to third line therapy was more effective and survival was improved from the time of first line therapy relapse among second line responders than that in nonresponders. Our data support the notion that second line responders are androgen independent but still hormonally sensitive.
Kojima
Satoko
S
Department of Urology, Graduate School of Medicine, Chiba University, Japan.
Suzuki
Hiroyoshi
H
Akakura
Koichiro
K
Shimbo
Masaki
M
Ichikawa
Tomohiko
T
Ito
Haruo
H
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; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology; D015996:Survival Rate; D014105:Tosyl Compounds; D017211:Treatment Failure
D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide