In: Disease11 May 2010
Long-Acting LH-RH Agonist Depot (Leuprolide Acetate) for Prostate Cancer
Speaker: Robert C. Tyler, MD, Director of Clinical Research, Atrix Laboratories, Inc., Fort Collins, Colorado.
A new six-month subcutaneous (SC) depot of leuprolide acetate (Eligard®, Atrix Laboratories, Inc.), a synthetic luteinizing hormone-releasing hormone (LH-RH) agonist, consistently produced and maintained safe and effective serum testosterone suppression. Total serum testosterone concentrations were well below the medical castrate level of less than 50 ng/dl in adult men.
Because treatment strategies to increase symptom-free survival in patients with advanced disease focus on testosterone suppression to ameliorate symptoms and control disease, a multicenter, open-label study was designed to assess the safety, efficacy, and pharmacokinetics of leuprolide acetate. A total of 111 patients received two SC injections of leuprolide depot 45 mg at 0 and six months over a 12-month period. Safety and efficacy, as measured by testosterone suppression and prostate-specific antigen (PSA) levels, were evaluated.
Of the 111 patients, 103 (93%) completed the 12-month study. Overall, mean and median times to castrate suppression were 21.2 and 21 days, respectively. At the completion of the study, 99% of patients had testosterone concentrations that were below castrate levels (12.3 ±2.1 ng/dl). Mean PSA levels decreased by 97%, from 39.8 ± 21.5 ng/ml at baseline, to 1.2 ± 0.3 ng/ml at 12 months. There were no clinically significant flare reactions. The most common treatment-related adverse drug event (ADE) was mild-to-moderate hot flashes.
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Bisphosphonic Acid Compound (Zoledronic Acid) for Bone Metastases in Hormone-Refractory Prostate Cancer
Speaker: Charles Metzger, MD, Urologist, Citrus Valley Uro-logic Medical Group, Glendora, California.
Zoledronic acid (Zometa®, Novartis), a bisphosphonic acid that inhibits osteoclastic bone reabsorption, is well known for reducing skeletal complications of bone metastases in men with hormone-refractory prostate cancer. This agent is effective in increasing bone mineral density in hormone-sensitive prostate cancer patients with bone metastases.
A prospective, open-label, multicenter clinical trial involved 221 men with advanced prostate cancer and documented bone metastases who were already receiving or just beginning hormonal therapy. The men received zoledronic acid 4 mg as a single 15-minute intravenous (IV) infusion every three weeks, for a maximum of 16 infusions. The primary endpoint of the study was the percentage of change from baseline of the lumbar (L) spine bone mineral density, measured at L2 to L4. Secondary endpoints included bone mineral density of the hip; changes in W-telopeptide and in bone-specific alkaline phos-phatase, which are known markers of bone remodeling; the time to the first skeletal event; and safety.
A total of 202 evaluable patients were in the intent-to-treat (ITT) group for efficacy analysis. Overall, there was a mean increase of 7.7% in bone mineral density in the lumbar spine at one year. Hip bone mineral density also increased by 3.6% at one year. Both W-telopeptide and bone-specific alkaline phosphatase decreased significantly from baseline to the final patient visit (P < .001). A single skeletal event was reported in 8.9% of the patients, and 3% of the patients had multiple skeletal events.
In general, zoledronic acid was safe and well tolerated. As expected, the most common ADEs were arthralgia, nausea, fatigue, back pain, bone pain, and anemia.
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