An investigational gonadotropin-releasing hormone blocker produces an almost immediate reduction in the testosterone levels of patients undergoing treatment for prostate cancer.
Orlando, FL-An investigational gonadotropin-releasing hormone blocker has been shown to produce an almost immediate reduction in the testosterone levels of patients undergoing treatment for prostate cancer. This can present an advantage compared to current LHRH agonists, which typically produce an initial flare of testosterone in patients.
Laurence Klotz, MD, chief of the division of urology at Sunnybrook Health Sciences Centre, Toronto, presented the results of the phase III study during the late-breaking science forum at the 2008 AUA annual meeting.
"This drug produces sustained, rapid reductions in testosterone, with no evidence of a testosterone flare," he said. "That makes it appealing."
Patients had histologically confirmed adenocarcinoma of the prostate for which androgen ablation was indicated, and patients requiring neoadjuvant hormonal therapy were excluded. Each group of patients had similar baseline characteristics, including age, weight, body mass index, cancer stage, Gleason score, PSA, and testosterone level.
The researchers considered a testosterone level of ≤.5 ng/mL from day 28 through day 364 a successful response to the therapies. Twenty-eight days after the initial injection, patients in the degarelix arms experienced a similar treatment response to the patients receiving leuprolide: 98.3% and 97.2% versus 96.4%. However, it was during the first 28 days of the study that the patients receiving degarelix responded differently than those receiving leuprolide.
Of the 201 leuprolide patients, 161 experienced a testosterone surge after the initial injection. Eight patients (5%) experienced an increase of >.25 ng/mL, four of whom reached values above .5 ng/mL. The median increase in testosterone at day 3 was 65%. The median testosterone level returned to baseline around day 7.
In the degarelix arms, by day 3, 97% of patients in the 160-mg arm and 96% of patients in the 80-mg arm had achieved the goal endpoint of suppression of testosterone levels to ≤.5 ng/mL. By day 14, 100% of patients in the degarelix arms achieved this endpoint, compared to 18.2% of patients in the leuprolide arm.
More rapid PSA decline
Patients in the degarelix arms also experienced a more rapid reduction in PSA than did patients in the leuprolide arm. After 14 days, median PSA in the degarelix patients (160 mg and 80 mg) had declined by 65% and 64% respectively, compared to a decline of 18% in the patients in the leuprolide arm at the same point. Patients in the degarelix, 80 mg, group also had a lower incidence of PSA failure (two consecutive increases of 50% and at least 5 ng/mL compared to nadir) than the other arms: 8.9% versus 14.2% in the degarelix, 160 mg, arm and 14.1% in the leuprolide arm.
During a question-and-answer period, Dr. Klotz was asked whether degarelix is clinically necessary.
"Back when leuprolide was released, if we were comparing head to head a drug that induced a flare [in testosterone] and a drug that did not, we would pick the drug that doesn't produce the flare," he said. "We don't want the flare-it's something we put up with. So degarelix is appealing in that it doesn't induce it."
In comparing adverse events, the patients in the degarelix arms experienced a higher percentage of injection site-related problems than did the leuprolide patients (44% and 35% vs. <1%). Other adverse event rates were similar among all arms. Five patients in each of the degarelix arms died, and nine patients died in the leuprolide group.
One of the authors of this study is an employee of Ferring Pharmaceuticals, and another author is a paid consultant to the company.