Rapamycin worldwide, cancer is hormone therapy, achieved either surgically with accounting for nearly a fifth of all newly diagnosed male bilateral orchidectomy or medically with luteinising cancers. In the UK, roughly men are diagnosed hormone releasing hormone agonists or with prostate cancer each year, and in almost antagonists, or oral,3 with additional 10 000 men died from the disease.1 Globally, cases radiotherapy for locally advanced cases. Hormone were diagnosed in The current standard fi rst-line therapy produces responses in up to of patients, but it is not curative and disease recurs in nearly all patients; median time to progression is estimated as months, driven by metastatic cases,3 and is longer in patients with locally advanced disease.
4,5 Such disease is referred to as hormone-refractory prostate cancer, or increasingly as castrate-refractory prostate cancer, although androgen-deprivation-refractory prostate can cer might be a preferable term. In that Rutin inhibitor setting, there is now a range of systemic treatments, including further hormonal manipulations,6 bisphosphonates,7 cytotoxic chemotherapy, 8 radionuclides,9 immunotherapy,10 and newer hormone therapies.11 The traditional approach is to assess new treatments for prostate cancer in castrate-refractory disease. An alternative approach is to inves tigate new drugs and new approaches to treatment as fi rst-line therapy in patients starting hormone therapy. At this point, patients are potentially fitter and better able to tolerate treatment, and intervention in the hormone-naive setting might have a better and more durable eff ect.
The STAMPEDE trial or Metastatic Prostate SNX-5422 908115-27-5 cancer: Evaluation of Drug Efficacy; Medical buy Hesperidin Research Council is an innovative, multiarm, multistage, multicentre, randomised controlled trial. We designed the trial to assess the effects of a bisphosphonate, a cytotoxic chemotherapy drug and a cyclo-oxygenase-2 inhibitor , as single agents or combinations, in patients starting hormone therapy for locally advanced or metastatic prostate cancer. The trial is designed with separate stages focusing on safety, activity, and efficacy data; a research arm is only allowed to proceed to the final stage of recruitment if the study treatment is shown to be acceptably safe and sufficiently active. We refer to lack of sufficient activity as lack of benefi t.
COX-2 is an isoenzyme induced by various mitogens, cytokines, and growth factors that are associated with a range of processes including infl ammation12 and carcinogenesis.13,14 Various case-control studies have shown social roles a reduction in risk of prostate cancer associated with the use of non-steroidal anti-infl ammatory drugs , which include inhibition of COX-2 among their mode of action.15 Pathological studies show that COX-2 is upregulated in carcinomas,16 and one study suggested that NSAID use might delay progression from subclinical to clinical prostate cancer.17 This combination of preclinical and epidemiological data justifi ed assessment of a COX-2 inhibitor in the present trial. The trial development group chose to assess the selective COX-2 inhibitor, celecoxib, because data suggest that it is better tolerated than other NSAIDs, exhibits activity as a cancer- preventing agent,18 and shows inhibition of angiogenesis and induction of apoptosis in human cancer cells including prostate cancer,19 particularly at higher doses.20 This decision was taken after full consideration of the risks and benefits.