TY - JOUR
T1 - Intermittent androgen suppression for rising PSA level after radiotherapy
AU - Crook, Juanita M.
AU - O'Callaghan, Christopher J.
AU - Duncan, Graeme
AU - Dearnaley, David P.
AU - Higano, Celestia S.
AU - Horwitz, Eric M.
AU - Frymire, Eliot
AU - Malone, Shawn
AU - Chin, Joseph
AU - Nabid, Abdenour
AU - Warde, Padraig
AU - Corbett, Thomas
AU - Angyalfi, Steve
AU - Goldenberg, S. Larry
AU - Gospodarowicz, Mary K.
AU - Saad, Fred
AU - Logue, John P.
AU - Hall, Emma
AU - Schellhammer, Paul F.
AU - Ding, Keyue
AU - Klotz, Laurence
PY - 2012/9/6
Y1 - 2012/9/6
N2 - BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P = 0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.)
AB - BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P = 0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.)
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Androgen Antagonists/administration & dosage
KW - Chemotherapy, Adjuvant
KW - Drug Administration Schedule
KW - Follow-Up Studies
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Proportional Hazards Models
KW - Prostate-Specific Antigen/blood
KW - Prostatic Neoplasms/drug therapy
KW - Quality of Life
KW - Testosterone/blood
UR - http://www.scopus.com/inward/record.url?scp=84865695405&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1201546
DO - 10.1056/NEJMoa1201546
M3 - Article
C2 - 22931259
AN - SCOPUS:84865695405
SN - 0028-4793
VL - 367
SP - 895
EP - 903
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 10
ER -
