Cetrorelix Shows Promise in BPH

NEW YORK — A new treatment paradigm for benign prostatic hyperplasia is on the horizon.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Herbert Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for α-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including loss of libido and erectile dysfunction. Moreover, compliance with daily regimens has been low, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH uses a gonado- tropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The GnRH antagonist is used to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, said Dr. Lepor, professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12. In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo. Improvements on IPSS of three to four symptom units were already noted at week 4. Mean baseline flow rate was about 9 ng/mL and rose to about 13 ng/mL in those in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%, and returned to baseline after the last injection. There was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. Doses were given at 14-day intervals. The results echoed those in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen.

A phase III study randomizing patients with BPH and voiding symptoms to cetrorelix pamoate is underway. Dr. Lepor disclosed he is a consultant to Æterna Zentaris Inc., the study sponsor.

NEW YORK — A new treatment paradigm for benign prostatic hyperplasia is on the horizon.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Herbert Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for α-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including loss of libido and erectile dysfunction. Moreover, compliance with daily regimens has been low, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH uses a gonado- tropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The GnRH antagonist is used to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, said Dr. Lepor, professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12. In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo. Improvements on IPSS of three to four symptom units were already noted at week 4. Mean baseline flow rate was about 9 ng/mL and rose to about 13 ng/mL in those in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%, and returned to baseline after the last injection. There was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. Doses were given at 14-day intervals. The results echoed those in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen.

A phase III study randomizing patients with BPH and voiding symptoms to cetrorelix pamoate is underway. Dr. Lepor disclosed he is a consultant to Æterna Zentaris Inc., the study sponsor.

NEW YORK — A new treatment paradigm for benign prostatic hyperplasia is on the horizon.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Herbert Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for α-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including loss of libido and erectile dysfunction. Moreover, compliance with daily regimens has been low, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH uses a gonado- tropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The GnRH antagonist is used to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, said Dr. Lepor, professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12. In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo. Improvements on IPSS of three to four symptom units were already noted at week 4. Mean baseline flow rate was about 9 ng/mL and rose to about 13 ng/mL in those in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%, and returned to baseline after the last injection. There was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. Doses were given at 14-day intervals. The results echoed those in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen.

A phase III study randomizing patients with BPH and voiding symptoms to cetrorelix pamoate is underway. Dr. Lepor disclosed he is a consultant to Æterna Zentaris Inc., the study sponsor.