Less Frequent Dosing of Drug for Patients with Bone Metastases Does Not Increase Risk of Fracture, Other Bone-related Events

Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, use of the bisphosphonate drug zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years, according to a study appearing in the January 3 issue of JAMA.

Bone involvement in metastatic cancer is a common clinical problem. Zoledronic acid administered intravenously every 3 to 4 weeks reduces pain and the incidence of skeletal-related events, including clinical fracture, spinal cord compression, radiation to bone, and surgery to bone by 25 to 40 percent. Bisphosphonates are generally well tolerated, but are associated with toxic effects, including osteonecrosis (severe bone disease that results from disrupted blood supply) of the jaw, toxicity in the kidneys, and abnormally low levels of calcium in the blood. The optimal dosing interval for zoledronic acid has not been determined. In this study, Andrew L. Himelstein, M.D., of the Helen F. Graham Cancer Center & Research Institute, Newark, Del., and colleagues randomly assigned 1,822 patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.

Among the patients who were randomized, 795 completed the study at 2 years. A total of 260 patients (29.5 percent) in the zoledronic acid every 4-week dosing group and 253 patients (28.6 percent) in the every 12-week dosing group experienced at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years of randomization. The proportions of skeletal-related events did not differ significantly between groups. Pain scores, incidence of jaw osteonecrosis, and kidney dysfunction also did not differ significantly between the treatment groups.

“This longer interval may be an acceptable treatment option,” the authors write.

(doi:10.1001/jama.2016.19425;