Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases
| العنوان: | Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases |
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| المؤلفون: | Hironobu Minami, Kan Yonemori, Yasuhiro Fujiwara, Masayuki Ohkura, Hirofumi Fujii, Winnie Sohn, Tatsuhiro Arai, Koichi Kitagawa, Tomoko Ohtsu |
| المصدر: | Cancer Science. 99:1237-1242 |
| بيانات النشر: | Wiley, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Cancer Research, medicine.medical_specialty, Anemia, Injections, Subcutaneous, Bone Neoplasms, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Gastroenterology, Collagen Type I, Cohort Studies, Breast cancer, Japan, Pharmacokinetics, Internal medicine, Biomarkers, Tumor, medicine, Humans, Bone Resorption, Adverse effect, Aged, Dose-Response Relationship, Drug, business.industry, Bone cancer, RANK Ligand, Antibodies, Monoclonal, Bone metastasis, General Medicine, Middle Aged, medicine.disease, Surgery, Denosumab, Oncology, Creatinine, Pharmacodynamics, Female, Peptides, business, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2008.00803.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2bc361b14df5a50b67b641c6e8cde365 https://doi.org/10.1111/j.1349-7006.2008.00803.x |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2bc361b14df5a50b67b641c6e8cde365 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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| DOI: | 10.1111/j.1349-7006.2008.00803.x |