Longer Dosing Interval for Zoledronic Acid for Bone Mets

Roxanne Nelson, BSN, RN

January 03, 2017

Longer dosing intervals do not appear to affect the efficacy of the bisphosphonate drug zoledronic acid (Zometa, Novartis) when used for the treatment of bone metastases, according to new findings published January 3 in JAMA.

Among cancer patients with bone metastases, zoledronic acid given every 12 weeks, as compared with the standard dosing interval of every 4 weeks, did not result in an increased risk for skeletal-related events during a 2-year period.

In addition, patients appeared to be more adherent to treatment on the 12-week schedule, and fewer patients developed osteonecrosis of the jaw.

"This longer interval may be an acceptable treatment option," conclude the authors, led by Andrew L. Himelstein, MD, from the Helen F. Graham Cancer Center and Research Institute, Newark, Delaware.

Zoledronic acid received approval from the US Food and Drug Administration for the treatment of bone metastases in patients with multiple myeloma and solid tumors. It is typically given every 3 to 4 weeks. Studies have shown that it reduces pain and the incidence of skeletal-related events by about 25% to 40%, note the authors.

Although bisphosphonates are generally well tolerated, associated side effects have been reported, including osteonecrosis of the jaw, nephrotoxicity, and hypocalcemia. The risk for osteonecrosis of the jaw increases with cumulative drug exposure, the authors add.

For this study, they hypothesized that zoledronic acid given every 12 weeks for 2 years would be noninferior to dosing at the standard interval of every 4 weeks. And after 2 years of such treatment, that is indeed what they found.

The cohort included 1822 patients with metastatic breast or prostate cancer or multiple myeloma in whom there was at least one site of bone involvement.

A total of 260 patients (29.5%) in the every-4-week dosing group and 253 patients (28.6%) in the every-12-week group developed at least one skeletal-related event within the defined period. These results met criteria for noninferiority.

The mean number of skeletal-related events per year (skeletal morbidity rate) was 0.4 for both groups. Pain and performance status scores were similar between the two groups.

Osteonecrosis of the jaw occurred in 18 patients (2.0%) in the group taking the drug every 4 weeks and in nine patients (1.0%) in the group taking the drug every 12 weeks.

Adherence to the treatment schedule was better among patients who took the drug every 12 weeks, note the authors. For these patients, 63% had no treatment delays, compared with 38% of the group taking the drug every 4 weeks.

The study was funded by grants from the National Cancer Institute. Coauthor Rui Qin, PhD, owns stock in Regeneron Pharmaceuticals, UnitedHealth Group, and Gilead Sciences, and coauthor Ann O'Mara, PhD, owns stock in Pfizer.

JAMA. 2017;317:48-58. Abstract


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