These results suggest that further studies of the effect of newer generation bisphosphonates on BPFS in men with metastatic prostate cancer are warranted.

Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). Results For both BPH and prostate cancer, COX-1 expression was primarily in the ®bromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was signi®cantly greater (P=0.008), with a change in the staining pattern from membranous to cytoplasmic (P<0.001). COX-2 expression was signi®cantly higher in poorly differentiated than in well differentiated tumours (P<0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. Conclusion This is the ®rst study to assess the coexpression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and signi®cantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-in¯am-matory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.

Objective To evaluate the eÃcacy and safety in a dosereductions in total symptom score were obtained with tamsulosin 0.4 mg and 0.6 mg (4.1, −28.7%, and ranging study of tamsulosin (once-daily) as a modifiedrelease formulation compared with placebo in patients 4.4 points, −28.2%, respectively) compared with reductions of 3.4 (−20.1%) in the tamsulosin with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and to estab-(0.2 mg) and 2.9 points (−17.7%) in the placebo groups. The diÂerence in eÂects on total symptom lish the optimum dosage for phase III clinical studies. Patients and methods Of 169 patients with LUTS associscore between treatment groups was not statistically significant, which can be attributed to the small ated with BPO enrolled in a 3 week placebo run-in period, 126 were subsequently randomized to receive sample size. Tamsulosin was well tolerated; at least one adverse event was reported by 29%, 23%, 27% placebo (28), or 0.2 mg (35), 0.4 mg (30), or 0.6 mg (33) of tamsulosin once daily for 4 weeks. Free-flow and 36% of patients in the placebo and tamsulosin 0.2 mg, 0.4 mg and 0.6 mg groups, respectively. There and pressure-flow measurements, and modified Boyarsky symptom scores were used to determine were no apparent tamsulosin dose-dependent changes in vital signs from baseline to the end of 4 weeks of eÃcacy. Safety was evaluated by monitoring adverse events and vital signs (including 8 h after the first randomized treatment. Tamsulosin caused no statistically significantly greater changes in blood pressure dose), and by laboratory determinations. Results Tamsulosin 0.4 mg and 0.6 mg produced sigthan placebo during the initial 8 h after the first dose. There were no clinically significant changes in laboranificantly greater improvements in maximum urinary flow rate (Q max ) (2.2 mL/s, 22.6%, and 1.8 mL/s, tory variables. Conclusion Tamsulosin is well tolerated and eÂective in 20.2%, respectively) than did placebo (−0.1 mL/s, −0.9%). The results from the pressure-flow studies improving urinary flow and relieving LUTS associated with BPO. Optimal eÂects are achieved with tamsuloconfirmed the results for Q max in the free flow studies, with optimum and significant eÂects for tamsin 0.4 mg administered once daily. Keywords Benign prostatic obstruction, tamsulosin, a 1 -sulosin 0.4 mg. This also applied for detrusor pressure at maximum flow, which decreased by 26.6 cmH 2 O adrenoceptor antagonists, a 1A -adrenergic receptor, lower urinary tract symptoms (−28.2%) on 0.4 mg tamsulosin whereas it increased by 4.9 cm H 2 O (5.7%) on placebo. Patients and methods [5][6][7]. This provides the rationale for using a 1 -adrenoceptor antagonists; they relax the bladder neck and This was a multicentre, double-blind, placebo-controlled, randomized phase II study involving 10 centres in the prostate smooth muscle and relieve the dynamic component of BPO, thereby increasing urinary flow and improv-UK. The study was approved by the local ethics committees and was performed in ...

Adjuvant sodium clodronate does not modify the natural history of nonmetastatic prostate cancer.