Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study.
OBJECTIVE
To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL).


METHODS
Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire.


RESULTS
Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up.


CONCLUSIONS
Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.
Department of Urology, Ichihara Hospital, Teikyo University School of Medicine, Chiba, Japan.
Naohide
N
Sato
Koichiro
K
Akakura
Shigeo
S
Isaka
Hiroomi
H
Nakatsu
Masashi
M
Tanaka
Haruo
H
Ito
Motoyuki
M
Masai
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000523:psychology / Q000556:secondary*; D000368:Aged; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D004334:Drug Administration Schedule; D005485:Flutamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000523:psychology / Q000556:secondary*; D010865:Pilot Projects; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood; D017211:Treatment Failure
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005485:Flutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide