Intermittent androgen suppression for locally advanced and metastatic prostate cancer: Preliminary report of a prospective multicenter study

• Published in: Urology (Ridgewood, N.J.) N.J.), 2004-08, Vol.64 (2), p.341-345
• Main Authors: Sato, Naohide, Akakura, Koichiro, Isaka, Shigeo, Nakatsu, Hiroomi, Tanaka, Masashi, Ito, Haruo, Masai, Motoyuki
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma - psychology; Adenocarcinoma - secondary; Aged; Androgens; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Disease Progression; Drug Administration Schedule; Flutamide - administration & dosage; Flutamide - therapeutic use; Follow-Up Studies; Gonadotropin-Releasing Hormone - agonists; Gynecology. Andrology. Obstetrics; Humans; Leuprolide - administration & dosage; Leuprolide - therapeutic use; Male; Male genital diseases; Medical sciences; Neoplasm Proteins - blood; Neoplasms, Hormone-Dependent - blood; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - psychology; Neoplasms, Hormone-Dependent - secondary; Nephrology. Urinary tract diseases; Pilot Projects; Prospective Studies; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - psychology; Quality of Life; Surveys and Questionnaires; Testosterone - blood; Treatment Failure; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2004.03.032

To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). 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. 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. 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.