Summary This report summarises the results of the clinical development program of zoledronic acid (Zometa ® ), a third generation bisphosphonate, in the management of metastatic bone disease that formed the basis for its approval in Europe for prevention of skeletal related events in patients with advanced malignancies involving bone. Three randomised, double-blind, controlled phase III trials were conducted in more than 3000 patients. In one study zoledronic acid was compared with the standard therapy, 90 mg pamidronate, in the treatment of osteolytic lesions in patients with multiple myeloma and breast cancer. Two other studies, one in bone metastatic prostate cancer patients and the other in patients with non small cell lung cancer and other tumour types, were placebo controlled. The results showed that zoledronic acid at the recommended dose of 4 mg infused over 15 minutes significantly reduced the risk of developing skeletal complications in breast cancer patients as compared to standard treatment with pamidronate and was at least as effective as pamidronate in patients with multiple myeloma. Furthermore it was the first bisphosphonate to demonstrate an objective clinical benefit as compared to placebo in patients with bone metastases from prostate, lung and other solid tumours. At the recommended dose the safety profile of the compound was similar to that of pamidronate. Based on its effectiveness, broad spectrum of activity, safety and convenience of administration zoledronic acid is expected to become an important and intergral part of the medical management of patients with bone metastasis. Epidemiology and pathophysiology of bone metastases Half of patients with cancer develop bone metastases in the course of their disease. Certain solid tumour types, particularly carcinomas of breast, lung and prostate, have a marked tropism for bone. These three malignancies together account for 80% of patients who have solid tumours metastatic to bone1. Other solid tumours that frequently spread to bone include thyroid and renal cancer1,2. Metastatic bone disease is a medical
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