132 Pooled analysis of two protocols of intermittent hormonal therapy, in advance prostatic cancer

Abstract

INTRODUCTION AND OBJECTIVES: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer. We present pooled results from two randomized trials which used similar protocols and had identical data collection and follow up management systems. The objective is to compare overall and cause specific survival between patients receiving intermittent therapy. METHODS: In MAB 626 patients (aged 50-88, mean 73), were randomized 314 to continuous therapy and 312 to intermittent. In CAB 917 patients (aged 44-81, mean 72) have been randomized 462 to Intermittent therapy and 455 to Continuous.The statistical analysis is through a pooled individual level meta analysis with interaction tests to assess the constancy of treatment comparisons across studies. In both protocols, patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a LHRH analogue plus 200 mg of CPA daily during induction. In both protocols, patients randomised to the continuous arm received the same treatment. MAB patients, in intermittent arm, when they are on treatment received the same scheme, while in CAB protocol, when on treatment received cyproterone acetate (CPA), 300 mg/daily. RESULTS: A total of 477 patients are known to have died in the MAB study and 525 in the CAB study. There was no evidence that the effect of intermittent therapy was different in the two studies and pooling the data is appropriate. There is no difference in overall survival: adjusting for study as the death rate in CAB is lower than in MAB, PSA, Metastatics Status, Gleason Score and Age, p 90, with hazard ratio (HR) 0.99 (95% CI 0.88 to 1.13). Patients who are M0, gleason less than 7 age 75 and randomization PSA 1ng/ml have a good prognosis and 213 (14%) patients are in this group. Among this group the hazard rate for continuous therapy compared to intermittent is 1.46 (95% CI 0.98, 2.18), p 0.065. Patients who are predicted to be off therapy for a long time are M0, randomization PSA 1ng/ml, gleason less than 7 but age 65-79. 269 (17%) of patients are in this group and Intermittent therapy is not significantly worse than Continuous therapy, p 0.38 HR 1.16 (95% CI 0.83, 1.63), for Continuous compared to Intermittent adjusting for study only. Sexual activity is better in the intermittent group. CONCLUSIONS: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, and better sexual activity. It may be particularly beneficial for patients who are good responders to therapy.