Denosumab was well tolerated and reduced bone resorption for at least 84 days

04-18-2006

A single dose s.c. of Denosumab was well tolerated and reduced bone resorption for at least 84 days in breast cancer patients.

According to a study from Belgium, "Receptor activator of nuclear factor-kappa B ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases."

"This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n=29) or multiple myeloma (n=25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels," wrote J.J. Body and colleagues, Institute Jules Bordet.

"The pharmacokinetics of denosumab also were assessed. Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated," they wrote.

"Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days," wrote J.J. Body and colleagues.

The researchers concluded: "The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate."

Body and colleagues published their study in Clinical Cancer Research (A study of the biological receptor activator of nuclear factor-kappa B ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res, 2006;12(4):1221-1228).

For more information, contact J.J. Body, Institute Jules Bordet, Dept. Med, Rue Heger Bordet 1, B-1000 Brussels, Belgium.

Publisher contact information for the journal Clinical Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: Brussels, Belgium, Breast Cancer, Breast Carcinoma, Medical Device, Monoclonal Antibody, Multiple Myeloma, Nuclear Factor, Oncology, Pharmacokinetic, Pharmacology, Women's Health.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.