Collective these data support the dings from our survey and suggest that both abiraterone acetate and MDV are likely to have a signi ant impact on UK clinical practice within the next years. Howev given this likely in x of new agents for CRPC in the near futu it will be important that oncologists work closely with urologists to further study the optimal GSK-3 Inhibitors sequencing of all treatments for mCRPC patients. Inde further ef acy and safety data from ongoing phase III studies of abiraterone acetate and MDV will likely determine the extent of use of these agents and their position in the sequencing of therapies in the futu and will also help to establish which patients will be treated with these agents and which will receive docetaxel. It is also worth noting th once availab these new therapies should be administered in dedicated uro-oncology clinics so that responses can be monitored accurately and the sequencing of these agents can continue to be monitored and optimized.
There was consensus among UK oncologists that the speci endothelin-A receptor antagoni zibotent and the anti-vascular endothelial growth factor monoclonal antibo bevacizum would not have an impact on the management of mCRPC in the futu with recent negative phase III study results identid as the reason for this. Inde although dings from a phase II study indicated that zibotentan is associated with improved overall survival pared with placebo in men with mCRPC , dings from a similar phase III study of zibotentan verses placebo failed to show a signi ant improvement in the primary endpoint of overall Pimecrolimus survival in men with mCRPC . Another phase III study BJU INTERNATIONAL THE AUTHORS BJU INTERNATIONAL OPTIMIZING THE MANAGEMENT OF ADVANCED PROSTATE CANCER IN THE UK has also recently been halted based on an early ef acy review by the Independent Data Monitoringmittee while indicated that zibotentan was unlikely to meet its primary ef acy endpoints in men with non-metastatic CRPC . A third phase III study of zibotentan inbination with docetaxel in chemotherapy-naive patients with mCRPC is still ongoing and results are expected later this ye but with two failed phase III studi the future of zibotentan as a treatment option in CRPC appears bleak.
Similar despite data from three phase II studies all suggesting that bevacizumab plus docetaxel is associated with encouraging anti-tumour activity in men with CRPC , results from a recent phase III study of bevacizumab plus docetaxel and prednisone showed that the addition of bevacizumab did not improve overall survival in men with mCRPC and was associated with increased morbidity and mortality . There were mixed views among UK oncologists regarding the future roles of custirsen and a?ibercept for the treatment of CRPC. Custirsen is an antisensense oligonucleotide that inhibits cluster a chaperone protein that protects cells from apoptosis-inducing stresso including cytotoxic chemothera and also inhibits mitochondrial apoptosis . A phase II randomized study showed that the allegiance addition of custirsen to docetaxel and prednisone was associated with improved overall survival and a favourable tolerability proe in men with mCRPC , and two phase III studies evaluating custirsen inbination with docetaxel and prednisone for the st-line.