Intermittent hormonal therapy in the treatment of metastatic prostate cancer: a randomized trial

OBJECTIVE To compare intermittent androgen deprivation therapy (ADT) and continuous ADT after 6 months of induction of ADT in patients with metastatic prostate cancer (PCa). PATIENTS AND METHODS This is an open-label randomized multi-centre study conducted in 58 centres in Europe. Patients with metastatic PCa and prostate-specific antigen (PSA) level >20 ng/mL at selection were randomized after 6 months of induction of ADT (leuprorelin and flutamide) if PSA level had decreased below 4 ng/mL. Patients received either continuous or intermittent ADT. All patients were treated until signs of disease progression under treatment or until study end with a monthly central PSA determination and follow-up visits were performed every 3 months. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, health-related quality of life (QLQ C30 questionnaire) and safety criteria. RESULTS Of 383 selected patients, 173 had a PSA level below 4 ng/mL after 6 months of induction of ADT and were randomized. Median overall survival (52 vs 42 months, P = 0.75) and median progression-free survival (15.1 vs 20.7 months, P = 0.74) were not significantly different between continuous and intermittent ADT. Although some differences in quality of life were observed, most of the functional and symptom scales showed no significant difference between the two groups. Significantly fewer treatment-emergent adverse events occurred in the intermittent group (P = 0.042), with the incidence of headache and hot flushes also lower. CONCLUSIONS This first randomized trial comparing continuous with intermittent ADT in metastatic PCa suggests that intermittent ADT might be as safe as continuous ADT. It could be an option in highly responding and well-informed patients even if no clear benefit in health-related quality of life was shown.