Phase III intermittent MAB vs continuous MAB

Patients with locally advanced or metastatic prostate cancer cannot be cured with any of the therapeutic tools available today. After an initial induction treatment of three months, with CPA 200 mg for two week's and then monthly depot injections of LHRH analogue (decaptyl) plus 200 mg of CPA daily in 766 patients with locally advanced or metastatic prostate cancer, 626 patients whose PSA decreased below 4 or to 80% below their initial value, were randomised to intermittent or continuous therapy. Among the 314 patients on Intermittent therapy, 50% have been off therapy for at least 52 weeks following the initial LHRH therapy, 29% have been off therapy for over 36 months. For the 197 patients whose PSA went down to 2 ng/ml, the median time off therapy was 74 weeks. When these patients returned to therapy they had a median of 14 weeks of treatment, followed by a second period off therapy, median 70 weeks. Patients with PSA < 2 ng/ml have spent a median of 82% of their time receiving no therapy.After a median follow up of 51 months, 321 patients have died: 162 in the Intermittent arm compared to 159 in the Continuous arm (HR = 1.03 [95% confidence interval 0.83, 1.28; p = 0.79]). Estimated survival at 5 years was 53.8% in the Intermittent Group and 51.0% in the Continuous Group.Subjective or Objective progression was noted in 224 patients, 113 on the intermittent arm and 111 on the continuous arm with a hazard ratio of 1.09 (95% CI 0.84, 1.42), p=0.52. The main differences in quality of life between the two arms of the study were confined to sexual function. Sexual activity was significantly greater (p<0.01) in the intermittent arm with 41% of men reporting sexual activity at 9 months, 40% at 15 months and 35% at 21 months.The most commonly reported side effects were hot flushes, were more frequently among those on Continuous Therapy, 30% of continuous patients compared to 20% of intermittent patients, p < 0.01. There is no evidence that Intermittent therapy leads to a significantly elevated hazard of dying (p = 0.79) or to a greater subjective or objective progression (p = 0.52) and with less impact on quality of live and less medication, patients with PSA < 2 ng/ml on randomisation have spent a median of 82% of their time receiving no therapy. We think that intermittent therapy is an option to use in regular clinic.