Zoledronic acid (Zometa) is an intravenously administered bisphosphonate that has been approved by the Food and Drug Administration (FDA) for the treatment of hypercalcemia of malignancy and bone mets of solid cancers. The 4mg monthly dose is the one FA indicated.
In two placebo-controlled clinical studies in patients with bone metastases from prostate cancer (n=643), meaning that 643 patien were enrollled on one arm, or from other solid tumors (n=773), meaning that 773 patietns were enrolled on the other arm, a large and meaningful study, both the percentage of patients with skeletal events (e.g., pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression) and the time to first skeletal event were decreased relative to placebo. This data was published and its size and prestige was accepted by FDA as a basis for approval and, therefore, general use. In these randomized controlled studies submitted to FDA for approval, there were 11 percent fewer skeletal events in zoledronic acid-treated patients with metastatic prostate cancer and 7 percent fewer skeletal events in treated patients with other metastatic solid tumors compared to placebo-treated patients. This was a statistically significant difference.
I underscore that all patients in these studies were prostate cancer patients.
The United States Pharmacopeial Convention has concluded that zoledronic acid has an established role in prophylaxis of drug-induced osteopenia secondary to androgen-deprivation therapy in prostate cancer patients (USPDI, 2005). The USPDI explains that long-term androgen deprivation therapy can lead to significant decreases in bone mineral density. Results of a multicenter, double-blind, placebo-controlled study demonstrated increased bone mineral density of the hip and spine of men with non-metastatic prostate cancer beginning androgen deprivation therapy plus zoledronic acid (4 mg IV every three months) for 1 year (Smith, et al., 2005). The USPDI notes that a smaller, open-label controlled trial, published in abstract form, demonstrated similar preliminary results.
Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy, which is the case here.
Ryan CW, Huo D, Demers LM, et al. Zoledronic Acid Initiated During the First Year of Androgen Deprivation Therapy Increases Bone Mineral Density in Patients with Prostate Cancer. Journal of Urology . 2006;178:972-978.
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Smith MR. Bisphosphonates to prevent skeletal complications in men with metastatic prostate cancer. J Urol. 2003;170(6 Pt 2):S55-S57; discussion S57-S58.
Saad F, Gleason DM, Murray R, et al. Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96(11):879-882.
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Van Poznak CH, Temin S, Yee GC, et al; American Society of Clinical Oncology. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol. 2011;29(9):1221-1227.
nccn, prostate cancer 2012