Bone Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Cancer, including details on symptoms, types, treatment. | ||||||||
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Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases.Yonemori K, Fujiwara Y, Minami H, Kitagawa K, Fujii H, Arai T, Sohn W, Ohkura M, Ohtsu T National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. kyonemor@ncc.go.jp Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B ligand (RANKL), suppresses bone resorption. This open-label, multicenter, phase 1 study evaluated the safety, pharmacodynamics, and pharmacokinetics of denosumab in Japanese women with breast cancer-related bone metastases. Patients (n = 18; median age, 57 years) received a single subcutaneous injection of denosumab 60 mg or 180 mg or three doses of denosumab 180 mg on days 1, 29, and 57 (every 4 weeks) and were followed for > or = 141 days. No major safety concerns related to denosumab were noted in any cohort. All patients experienced at least 1 adverse event (AE); most were mild (grade < or = 2). One patient reported grade 4 myositis and grade 3 anemia, malaise, and dysphagia that the investigator deemed treatment-related; other treatment-related AE were grade < or = 2. No antidenosumab antibodies or clinically significant changes in laboratory findings, vital signs, or electrocardiograms were observed. Pharmacokinetics were approximately dose-linear. Denosumab caused rapid, substantial, and sustained suppression of urinary N-telopeptide corrected for creatinine (uNTx/Cr) across all doses; at day 85, the median change from baseline uNTx/Cr ranged from -61.9% to -90.8%. No dose-limiting toxicity was observed at any dosage. Coupled with pharmacokinetic and pharmacodynamic data, these results were consistent with those observed in non-Japanese populations. Published 16 May 2008 in Cancer Sci, 99(6): 1237-42.
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