General Information

Zometa (zoledronic acid) is a bisphosphonate.

Zometa is a bisphosphonate indicated for the treatment of:

• Hypercalcemia of Malignancy
• 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.

Clinical Results

MM and bone metastases: The safety and effectiveness of Zometa was supported by three large international trials that included more than 3,000 subjects with multiple myeloma, breast cancer, prostate cancer, lung cancer and other solid tumors. The three trials consisted of a pamidronate-controlled trial in breast cancer and multiple myeloma, a placebo-controlled trial in prostate cancer, and a placebo-controlled trial in other solid tumors. Results demonstrated that Zometa decreased skeletal complications of subjects with multiple myeloma or metastases from solid tumors. In the two placebo-controlled trials, the number of subjects with skeletal events and the time to first skeletal-related event were both decreased compared to placebo.

HCM: Zometa was evaluated in two multicenter, randomized, double-blind trials in which it was compared to Aredia (pamidronate) 90 mg. The trials included 275 evaluable subjects, and treatment groups were generally well balanced in terms of age, sex, race and tumor types. Treatment with a single dose of either Zometa 4 mg or 8 mg was compared to a single dose of Aredia 90 mg.

Data revealed that the proportion of subjects with normalization of corrected serum calcium (CSC) by day 10 were 88% and 70% for Zometa 4 mg and Aredia 90 mg, respectively. The risk of renal toxicity with Zometa 8 mg was shown to be significantly greater than that seen with Zometa 4 mg - notably, no additional benefit was seen with the higher dosage.

Zometa also demonstrated positive results in secondary efficacy variables. Results showed that time to relapse was 30 days for Zometa 4 mg and 17 days for Aredia 90 mg. Duration of complete response, or the maintenance of normalized calcium levels, was 32 days for Zometa 4 mg and 18 days for Aredia 90 mg.

Side Effects

In general, adverse reactions to Zometa were mild and short-lived. Adverse events reported by subjects in clinical trials include (but are not limited to) the following:

• Fever
• Nausea
• Constipation
• Diarrhea
• Vomiting
• Abdominal pain
• Anemia

Zometa, like other bisphosphonates, has been associated with renal insufficiency.

Adverse events reported in clinical trials with Zometa include (but are not limited to) the following:

• Arthralgia (joint pain)
• Myalgia (muscle pain)
• Fatigue
• Gastrointestinal reactions
• Anemia
• Weakness
• Cough
• Dyspnea (difficult or labored breathing)
• Edema

Mechanism of Action

The principle pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. Zoledronic acid also blocks the osteoclastic resorption of mineralized bone and cartilage through its binding to bone. Zoledronic acid inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors. (from Zometa Prescribing Information).