Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group.

BACKGROUND: Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa).

OBJECTIVE: To determine whether intermittent therapy is associated with a shorter time to progression.

DESIGN, SETTING, AND PARTICIPANTS: 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment. The 626 patients whose prostate-specific antigen (PSA) level decreased to <4 ng/ml or to 80% below the initial value were randomised.

INTERVENTION: Patients received cyproterone acetate (CPA) 200mg for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH) analogue plus 200mg of CPA daily during induction. Patients randomised to the intermittent arm ceased treatment, while those randomised to the continuous arm received 200mg of CPA daily plus an LHRH analogue.

MEASUREMENTS: Primary outcome measurement was time to subjective or objective progression. Secondary outcomes were survival and quality of life (QoL). Time off therapy in the intermittent arm was also recorded.

RESULTS AND LIMITATIONS: 127 patients from the intermittent arm and 107 patients from the continuous arm progressed, with a hazard ratio (HR) of 0.81 (95% confidence interval [CI]: 0.63-1.05, p=0.11). There was no difference in survival, with an HR of 0.99 (95% CI: 0.80-1.23) and 170 deaths in the intermittent arm and 169 deaths in the continuous arm. The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41). Side-effects were more pronounced in the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 wk (95% CI: 39.4-65.7).

CONCLUSIONS: IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community.