hormone Abiraterone therapy were LHRH analogues, maximum androgen blockade, LHRH antagonists, orchidectomy, or, in patients without metastasis, bicalutamide monotherapy ; choice of hormone therapy was based on clinician and patient preference. Radiotherapy was encouraged for men with N0M0 disease , with a target window of 6–9 months after starting hormone therapy, so that radiotherapy could be given at the same time in all trial arms and patients would not have chemotherapy and radiotherapy concomitantly. Patients allocated to celecoxib were planned to receive one 400 mg capsule twice daily, taken orally, until 1 year or an FFS event. Patients were followed up every 6 weeks for 6 months, then every 12 weeks for 2 years, then every 6 months for 5 years, and annually thereafter.
PSA measurements were done at every follow-up; further tests were at the discretion of the treating clinician. Nadir PSA was considered the lowest value within 6 months on trial. HT=hormone therapy. FFS=failure-free survival. *Two patients Sesamin inhibitor were excluded from the activity Dihydroartemisinin 71939-50-9 analysis in arm A because of errors in event dates that were unresolved at the time of this intermediate analysis. Both patients reported FFS events before randomisation. .Patients are conservatively excluded from the safety analysis if they have not returned follow-up data or reported a serious adverse event; this is expected since accrual was ongoing at the time of analysis and some patients would not have reached their first on-trial assessment point.
Toxicities and symptoms were systematically reported at each buy Glycyrrhizic acid follow-up; serious adverse events and reactions were reported according to the National Cancer Institute Common Toxicity Criteria. The sample size was calculated using -nstage- and its predecessor programs. This program, which is implemented in Stata, is freely available23 and allows for the design of multiarm, multistage trials. We assumed, for the control arm, median FFS of 2 years and median overall survival of between 4 and 5 years, depending on patient mix. We targeted a 25% relative reduction in events for both FFS and survival; this translates to a 9% absolute improvement at the median time. Table 1 shows the trial design parameters, which start with a permissive alpha and become stricter over time.
These parameters were chosen to ensure that meaningful amounts of new data would be accumulated between intermediate analyses, which were triggered when specific numbers of social roles events had been reported in the control group. A one- sided test was chosen because research arms must pass an intermediate hurdle to continue accrual. The power was set high throughout the stages to avoid excluding an active research arm inappropriately. The overall alpha and power levels represent the values for each pairwise comparison of research arm against the common control arm, accounting for intermediate analyses and repeated use of the control arm. The statistical design parameters translate into a series of activity hurdles against which each research arm is compared at three predefi ned intermediate analyses.24 At the end of the second activity stage, reported here, the HR cutpoint was 0·924, determined with 95% power and a one-sided alpha of 0·25, with analyses planned for when roughly 216 FFS events had been reported in the control group. It was anticipated that research arms with an HR less favourable than the cutpoint would be considered as showing insufficient activity and accrual might therefore .