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An investigational vitamin D agonist significantly slowed prostate growth and improved prostate symptoms and urinary flow in men with symptomatic benign prostatic hyperplasia.
Orlando, FL-An investigational vitamin D agonist significantly slowed prostate growth and improved prostate symptoms and urinary flow in men with symptomatic BPH, data from a randomized clinical trial showed.
Prostate growth was reduced by as much as 85% with elocalcitol versus placebo, lead author Francesco Montorsi, MD, reported at the AUA annual meeting. The addition of the alpha-blocker tamsulosin (Flomax) did not improve on results achieved with the vitamin D agonist alone.
"The rate of prostate growth in the placebo group was in line with published literature," said Dr. Montorsi, associate professor of urology, University Vita-Salute San Raffaele in Milan, Italy. "The reduced rate of growth with elocalcitol shows that the drug can arrest prostate growth.
Elocalcitol is a non-hypercalcemic vitamin D agonist that demonstrated anti-inflammatory and antiproliferative activity in preclinical studies. In preliminary clinical studies, elocalcitol slowed prostate growth and improved bladder function, leading to the dose-finding study reported by Dr. Montorsi.
The study involved 542 men with a baseline prostate volume of 60 to 70 cc and an International Prostate Symptom Score (IPSS) of 16 to 17. Patients were randomized to placebo or to one of three active-treatment groups: elocalcitol, 75 mcg/day; elocalcitol, 150 mcg/day; or elocalcitol, 150 mg plus tamsulosin, 0.4 mg/day.
Treatment continued for 6 months, and the primary endpoint was change in prostate volume from baseline. Secondary endpoints included symptom improvement and change in flow rate (Qmax).
By the end of the study, total prostate volume increased by 3.52% in the placebo group, whereas prostate growth averaged 1.54% (p=.0135) in men treated with the lower dose of elocalcitol and 0.52% (p<.0001) in those treated with the higher dose. The addition of tamsulosin to the higher dose of elocalcitol was associated with an increase of 1.52% in total prostate volume (p=.0059) compared to placebo.
IPSS scores improved by five to six points in all treatment groups. Putting the results into perspective, Dr. Montorsi presented data on a subset of men who had IPSS scores >12, eight or more frequency episodes daily, and three or more urgency episodes daily. Men treated with the higher dose of elocalcitol had a seven-point improvement in baseline IPSS, comparable to the results observed in similar patients enrolled in a trial that evaluated the combination of tamsulosin and the antimuscarinic agent tolterodine (Detrol) (JAMA 2006; 296:2319-28).
"Investigators in that trial concluded that these types of patients might not respond to monotherapy with either an alpha-blocker or an antimuscarinic," Dr. Montorsi said.
The study population had a baseline Qmax of 10 to 11 mL/sec, which im-proved by one to two points in all treatment groups and did not differ among the groups. When the analysis was limited to men with IPSS >12, frequency 8+, and urgency 3+, the higher dose of elocalcitol monotherapy resulted in an improvement of 2.83 mL/sec, which proved to be significantly better than placebo (p=.03).
Another subset analysis limited to patients with IPSS >12 and 3+ urgency episodes at baseline demonstrated significant improvement in urgency with 150 mcg of elocalcitol (p<.01) and with the combination (p=.04).
"The magnitude of the effect of elocalcitol seems to be comparable to the effect in the [tamsulosin-tolterodine] study," said Dr. Montorsi.
Adverse events occurred less often in the elocalcitol monotherapy groups than in the placebo group, and the highest incidence of adverse events occurred with combination therapy. In particular, erectile dysfunction, retrograde ejaculation, and decreased libido occurred in one patient on elocalcitol monotherapy compared with three in the placebo group and six in the combination arm.
Dr. Montorsi is a scientific adviser for BioXell as well as a consultant/adviser to Pfizer.