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| |  FDA Approves Zometa (Zoledronic Acid) For Hypercalcemia of Malignancy EAST HANOVER, NJ -- August 21, 2001 -- Novartis announced today it has received marketing approval from the U.S. Food and Drug Administration for Zometa® (zoledronic acid for injection), a new generation intravenous bisphosphonate for the treatment of hypercalcemia of malignancy. Hypercalcemia of malignancy (HCM) is the most common life-threatening metabolic complication associated with cancer. Clinical trials demonstrated a statistically significant difference favoring Zometa when compared to the current treatment standard, Aredia®) (pamidronate disodium for injection), with respect to the proportion of complete responders. Response was measured by a normalization of corrected serum calcium by day 10. In addition, a 4 mg dose of Zometa offers the convenience of a 15-minute infusion time, as compared to two-to-24 hours for Aredia. "It is very encouraging to know that we have a new, effective treatment for HCM in the U.S. for such an important and potentially life-threatening cancer complication," said lead investigator Pierre Major, MD, Medical Oncologist at Hamilton Regional Cancer Center and Associate Professor in the Department of Medicine at McMaster University, Hamilton, Ontario, Canada. "It is likely that with its efficacy and shorter infusion time, Zometa should replace Aredia as the gold standard for HCM." Hypercalcemia of malignancy, which is characterized by elevated serum calcium levels, affects more than 10 percent of all cancer patients and generally occurs late in the course of the disease. It occurs when factors made by cancer cells over-stimulate cells called osteoclasts, which accelerate the breakdown of bone (resorption) and release excess calcium into the bloodstream. The resulting excessively high calcium levels overload the kidneys' processing capability. The calcium remains in the blood, which leads to potentially life-threatening complications such as dehydration, generalized muscle weakness, fatigue, nausea, vomiting, confusion, coma and even death. It appears most frequently in cases of breast cancer, multiple myeloma and non-small cell lung cancer. It may also occur in head and neck cancer, lymphoma, leukemia, kidney cancer and gastrointestinal cancer. The clinical data upon which the filing and subsequent approval were based are from two pivotal studies comparing Zometa to Aredia. The two multi-center trials enrolled 287 patients of which 275 patients met the evaluation criteria. Patients received a single dose of either Zometa 4 mg or Zometa 8 mg and were compared to patients receiving a single dose of Aredia 90 mg. By day 10 of treatment, corrected serum calcium concentrations were normalized in 88 percent of patients treated with Zometa 4 mg. In comparison, only 70 percent of patients treated with Aredia 90 mg achieved normalized serum calcium concentrations (p=0.002). The results of this trial have been published in the January 15, 2001 issue of the Journal of Clinical Oncology. In the patients taking Zometa, the median duration of complete response (maintaining normalized calcium levels) was 32 days for Zometa 4 mg, and 18 days for Aredia 90 mg. Time to relapse was 30 days for Zometa 4 mg and 17 days for Aredia 90 mg (p<0.05). There was no difference between the outcomes in the 4 mg versus 8 mg dose of the Zometa arm. To date, Novartis has received marketing clearances for Zometa for the treatment of HCM in the European Union, and more than 30 other countries, including Canada, Switzerland, Brazil and Australia. A supplemental application for Zometa for the treatment of bone metastases will be filed with the FDA shortly. The recommended dose of Zometa in hypercalcemia of malignancy is 4 mg. The 4 mg dose is given as a single-dose intravenous infusion over no less than 15 minutes. Patients must be adequately re-hydrated prior to administration of Zometa. Renal function must be carefully monitored in all patients receiving Zometa. In the HCM clinical trials, adverse reactions to Zometa were usually mild and transient and similar to those reported for other bisphosphonates. The most commonly associated adverse events included flu-like syndrome (fever, arthralgias, myalgias, skeletal pain), gastrointestinal reactions, anemia, insomnia and dyspnea. Occasionally, patients experienced electrolyte and mineral disturbances, such as low serum phosphate, calcium, magnesium and potassium. Bisphosphonates, including Zometa, have been associated with reports of renal function deterioration. Limited clinical data are available regarding use of Zometa in patients with renal impairment. Early experience with Zometa in clinical trials treating patients with bone metastases indicated that risk for renal function deterioration (defined as an increase in serum creatinine) is increased in patients who receive the drug over five minutes versus 15 minutes. In addition, the risk for renal function deterioration is increased in patients receiving the 8 mg dose of Zometa, even over 15 minutes. Patients who receive Zometa should have periodic evaluations of standard laboratory and clinical parameters of renal function. Doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. Zometa should be used with caution in patients with aspirin-sensitive asthma. Caution should also be exercised when Zometa is used in combination with loop diuretics due to an increased risk of hypocalcemia. Zometa should only be used during pregnancy if the potential benefit justifies the risk to the fetus. Zometa is contraindicated in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of Zometa. SOURCE: Novartis Oncology Related Link: Novartis.
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