Preclinical studies with
zoledronic acid (
Zometa; Novartis
Pharmaceuticals Corp, East Hanover, NJ) have shown its potential in malignant
bone disease. Clinical studies in the treatment of
hypercalcemia of
malignancy have been completed, as have phase I and II trials in patients with
cancer and pre-existing bone
metastases. Three randomized, double-blind, controlled phase III trials are ongoing to establish the efficacy and safety of
zoledronic acid in the treatment of osteolytic and osteoblastic bone
metastases. In one study, 4 mg
zoledronic acid is compared with the standard
therapy, 90 mg
pamidronate, in treatment of osteolytic lesions in patients with
breast cancer and
multiple myeloma. Two other studies, one in patients with
prostate cancer and bone
metastases and another in patients with
non-small cell lung cancer and other
tumor types, are placebo-controlled. The primary end point in all three studies is the frequency of skeletal complications resulting from bone
metastases. Adjuvant trials that assess the ability of
zoledronic acid to prevent or reduce the incidence of bone
metastases in patients at high risk for future skeletal
metastasis are also planned or ongoing. The rationale and design of these ongoing and planned studies is discussed.