ROCKVILLE, MarylandZometa (zoledronic acid for injection) has
received marketing approval from the US Food and Drug Administration for the
treatment of hypercalcemia of malignancy. Zoledronic acid represents a new
generation of intravenous bisphosphonates. It is currently approved for
treating hypercalcemia of malignancy in more than 30 countries.
Novartis has also filed an application with the FDA seeking approval for the
drug in treating bone metastases that occur as a result of a number of cancers.
These malignancies include prostate and lung cancer, for which no
bisphosphonate therapy is currently approved.
Hypercalcemia of malignancy is the most common life-threatening metabolic
complication associated with cancer, Novartis noted. Excessively high calcium
levelswhich result when factors produced by tumor cells overstimulate
osteoclastsaffect more than 10% of cancer patients, generally in the late
stages of their disease.
Zoledronic acid inhibits increased osteoclastic activity and the release of
skeletal calcium. If hypercalcemia of malignancy recurs, patients can be
treated again with the same zoledronic acid protocol.
The company submitted two pivotal studies comparing the drug with
pamidronate disodium for injection (Aredia), the current treatment standard
for hypercalcemia of malignancy.
The two international, multicenter trials enrolled a total of 287 patients
(275 evaluable). Patients were infused with a single dose of zoledronic acid,
at either 4 mg or 8 mg, or a single 90-mg dose of pamidronate delivered over 2
hours. Researchers measured clinical response by the normalization of corrected
serum calcium by day 10.
Pooled results of the two studies showed that by day 10, 88% of the patients
who received zoledronic acid 4 mg had normal corrected serum calcium
concentrations, compared with 70% of those treated with pamidronate (P = .002).