poor prognosis, requiring long-term hormone therapy, and to test the hypothesis that interventions at the point of fi rst hormone manipulation improve long-term outcome. The trial is predicated on the notion that high-risk prostate cancer includes a range of patients, from those with localised disease and poor prognostic characteristics to those presenting with metastatic disease, and Sunitinib that current therapies have limited long-term efficacy in many cases. The original statistical design therefore assumed a median FFS time of around 2 years; this estimation has been validated by the data presented here. Median overall survival was assumed to be twice the median FFS, although there have been too few deaths to estimate this accurately.
It seems likely that median survival will be higher than originally anticipated, which might be partly related to new, active therapies that patients Sodium Danshensu 14a-demethylase inhibitor can receive after their first trial FFS event. These therapies include docetaxel,32,33 which has entered standard practice for treatment of later stages of prostate cancer since the trial was launched. Further agents are emerging, including abiraterone,34 cabazitaxel,35 sipuleucel-T,10 radium-223,36 and MDV3100.37,38 With the recent demonstration of a survival benefit with radical radiotherapy in patients with Naringin 10236-47-2 locally advanced disease,4,5 we anticipate further improve ments in FFS and overall survival; indeed, the trial was amended in November, 2011, to mandate the use of radiotherapy in newly diagnosed N0M0 disease following these results.5 The accumulating event rate is monitored as part of trial oversight processes.
The remaining trial arms continue to recruit new patients and their buy Dihydroartemisinin data remain masked. Researchers might infer that there is at least some evidence of improved FFS in these arms, but such evidence is not suffi cient to stop or change the trial. A further change to the trial occurred in November, 2011, with the intro duction of hormone therapy plus abiraterone as a new research arm. Patients in the new arm will only be compared with those randomised contemporaneously to the control group. The trial can adaptively introduce further research arms and stop early those arms showing a lack of benefi t.24 Further research arms are likely to be introduced into the trial. The practical issues in handling the early stopping of the celecoxib-containing arms and the addition of further research arms will be discussed in a separate paper.
In conclusion, we have shown that celecoxib given 400 mg twice daily for 1 year is insufficiently active for men starting long-term therapy for high-risk prostate cancer, and we do not recommend its use in this setting. Medical Research Council employees. MKBP has received honoraria from Sanofi-Aventis for membership of an independent data monitoring committee. occupation NDJ has served on advisory boards for Sanofi-Aventis, Novartis, and Pfizer. MDM has received honoraria and expenses for advisory boards and lectures from Sanofi-Aventis. DPD has served on advisory boards for Novartis. GB has served on advisory boards for Sanofi-Aventis, Novartis, and Pfi zer, and received speaker’s fees from Sanofi-Aventis. AJB has received speaker’s fees from Sanofi-Aventis, Novartis, and Pfizer, and served on advisory boards for Sanofi-Aventis. JMOS has served on advisory boards and received speaker’s fees from Sanofi-Aventis. AP has received speaker’s fees and honoraria for advisory boards from Pfizer. DS has received conference fees.