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. Clinical trials demonstrated a statistically significant
difference in the number of complete responses among patients receiving
zoledronic acid compared to those receiving the current standard treatment,
pamidronate (Aredia). Response was measured by a normalization of serum calcium
by day 10.
"It is very encouraging to know that we have a new,
effective treatment for hypercalcemia of malignancy in the United States 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
hypercalcemia of malignancy."
The clinical data upon which the filing and subsequent
approval were based were from two pivotal studies that compared zoledronic acid
to pamidronate. The two multicenter trials enrolled 287 patients, of which 275
were evaluable. Patients were randomized to receive a single dose of either
zoledronic acid at 4 mg or 8 mg or a single dose of pamidronate at 90 mg. By day
10 of treatment, serum calcium concentrations were normalized in 88% of patients
treated 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 patients
taking zoledronic acid at 4 mg was 32 days vs 18 days for patients receiving
pamidronate. Time to relapse was 30 days for the zoledronic acid arm and 17 days
for the pamidronate arm (P < .05). There was no difference in
outcome between the 4-mg and 8-mg dose arms.
The most common adverse events associated with the use of zoledronic acid
included 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 serum
phosphate, calcium, magnesium, and potassium.