acid (Zo-meta) reduces the incidence of skeletal-related events (SREs) such as
bone pain and pathologic fractures in patients with bone metastases from
prostate and other solid tumors, researchers reported at two major medical
In a study of patients with non-small-cell lung cancer (NSCLC)
and other solid tumor metastases, zoledronic acid reduced by nearly 20% the
proportion of patients who had SREs, Lee Rosen, MD, reported at the 38th Annual
Meeting of the American Society of Clinical Oncology (abstract 1179). Fred Saad,
MD, reported at the 97th Annual Meeting of the American Urological Association
(abstract 703) that the drug had similar effects in prostate cancer patients
with bone metastases. Both studies were sponsored by Novartis Oncology.
Solid Tumor Study
Dr. Rosen, formerly of UCLA’s Jonsson Comprehensive Cancer
Center and currently director of developmental therapeutics, Cancer Institute
Medical Group, Santa Monica, California, described a phase III study that
compared placebo with two different doses of zoledronic acid in patients with
bone metastasis from solid tumors other than breast or prostate cancer.
"We are all aware of the skeletal complications of advanced
solid tumors, and of the vicious cycle of bone destruction, morbidity, and
mortality often seen in these patients," Dr. Rosen said. "The bisphosphonates
preferentially bind to bone, shorten the natural life of osteoclasts, and
reduce the interactions between osteoclasts and tumors. The
aminobisphosphonatespamidronate [Aredia] and zoledronic acidalso inhibit
tumor invasion and adhesion to the bone matrix, as well as inducing apoptosis
in tumor cell lines."
The trial had been designed as a three-arm study to include
randomization to placebo, 4 mg, or 8 mg of zoledronic acid given as a 5-minute
infusion every 3 weeks for 9 months. Because of renal toxicity, the infusion
period was lengthened to 15 minutes and infusion volume was increased from 50
mL to 100 mL. Because this did not completely solve the problem, the 8-mg
zoledronic acid arm was reduced to 4 mg.
All 773 patients enrolled had at least one documented bone
metastasis. Patients were stratified by whether they had lung cancer (51%,
primarily non-small cell) or other solid tumors (including renal, unknown
primary, and bladder cancer). An SRE was defined as a pathologic fracture,
spinal cord compression, need for radiation therapy to bone to relieve pain,
surgery to bone, or hypercalcemia of malignancy.