FDA Approves Zoledronic Acid for the Treatment of Hypercalcemia of Malignancy

October 1, 2001

Novartis announced recently that it received marketing approval from the US Food and Drug Administration (FDA) for zoledronic acid (Zometa), a new generation intravenous bisphosphonate for the treatment of hypercalcemia of malignancy.

Novartis announced recently that it received marketingapproval from the US Food and Drug Administration (FDA) for zoledronic acid (Zometa),a new generation intravenous bisphosphonate for the treatment of hypercalcemiaof malignancy. Clinical trials demonstrated a statistically significantdifference in the number of complete responses among patients receivingzoledronic acid compared to those receiving the current standard treatment,pamidronate (Aredia). Response was measured by a normalization of serum calciumby day 10.

"It is very encouraging to know that we have a new,effective treatment for hypercalcemia of malignancy in the United States forsuch an important and potentially life-threatening cancer complication,"said lead investigator Pierre Major, MD, medical oncologist at Hamilton RegionalCancer Center and associate professor in the department of medicine at McMasterUniversity, Hamilton, Ontario, Canada. "It is likely that with its efficacyand shorter infusion time, Zometa should replace Aredia as the gold standard forhypercalcemia of malignancy."

Trial Data

The clinical data upon which the filing and subsequentapproval were based were from two pivotal studies that compared zoledronic acidto pamidronate. The two multicenter trials enrolled 287 patients, of which 275were evaluable. Patients were randomized to receive a single dose of eitherzoledronic acid at 4 mg or 8 mg or a single dose of pamidronate at 90 mg. By day10 of treatment, serum calcium concentrations were normalized in 88% of patientstreated with zoledronic acid at 4 mg. Among patients treated with pamidronate,only 70% achieved normalized serum calcium concentrations (P = .002).The results of this trial were published in the January 15, 2001, issue of the Journal of Clinical Oncology.

The median duration of complete response among patientstaking zoledronic acid at 4 mg was 32 days vs 18 days for patients receivingpamidronate. Time to relapse was 30 days for the zoledronic acid arm and 17 daysfor the pamidronate arm (P < .05). There was no difference inoutcome between the 4-mg and 8-mg dose arms.

Adverse Events

The most common adverse events associated with the use of zoledronic acidincluded a flu-like syndrome (fever, arthralgias, myalgias, skeletal pain),gastrointestinal reactions, anemia, insomnia, and dyspnea. Occasionally,patients experienced electrolyte and mineral disturbances, such as low serumphosphate, calcium, magnesium, and potassium.