Intermittent androgen suppression in the treatment of prostate cancer: a preliminary report.
OBJECTIVE
To test the feasibility of using intermittent androgen suppression in the treatment of prostate cancer by taking advantage of the reversible action of medical castration.


METHODS
Observations were made on a group of 47 patients (clinical Stage D2, 14; D1, 10; C, 19; B2, 2; and A2, 2) with a mean follow-up time of 125 weeks. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Medication was then withheld until the serum PSA increased to a mean value between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of serum PSA became androgen independent.


RESULTS
The first two treatment cycles lasted 73 and 75 weeks, with a mean time off therapy of 30 and 33 weeks and an overall mean percentage time off therapy of 41% and 45%, respectively. The mean time to achieve a nadir level of serum PSA was 20 weeks in cycle 1 and 18 weeks in cycle 2. Serum testosterone returned to the normal range within 8 weeks (range, 1 to 26) of stopping treatment. The off-treatment period in both cycles was associated with an improvement in sense of well-being and the recovery of libido and potency in the men who reported normal or near-normal sexual function before the start of therapy. In 7 patients with Stage D2 disease, the cancer progressed to an androgen-independent state. The mean and median times to progression were 128 weeks and 108 weeks, respectively. Seven patients have died, 1 from a noncancer-related illness, with mean and median overall survival times of 210 weeks and 166 weeks, respectively.


CONCLUSIONS
Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy. It also results in reduced toxicity and cost of treatment and possibly delays tumor progression. Whether survival is affected in a beneficial or adverse way remains to be studied in a randomized, prospective study.
Goldenberg
S L
SL
Department of Surgery, University of British Columbia, Vancouver, Canada.
Bruchovsky
N
N
Gleave
M E
ME
Sullivan
L D
LD
Akakura
K
K
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D017373:Cyproterone Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D004054:Diethylstilbestrol / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D017273:Goserelin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors
D000726:Androgen Antagonists; D017273:Goserelin; D017373:Cyproterone Acetate; D004054:Diethylstilbestrol; D017430:Prostate-Specific Antigen; D016729:Leuprolide