SynthesisBritish journal of clinical pharmacology2014
The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review.
Synthesis in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer.Scientific reports · 2020Trial
- Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial.Blood advances · 2018Trial
- Calculating Receptor Occupancy using TMDD Models - What has to be Considered?The AAPS journal · 2026Article
- [Expert consensus on perioperative management of tooth extraction in patients receiving denosumab therapy].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Article
- Successful prevention of medication-related osteonecrosis of the jaw after dental extractions by socket preservation with alloplast plus tetracycline in patients taking antiresorptive drugs.Journal of dental sciences · 2026Article
- Trends in serum phosphate, calcium, and parathyroid hormone levels according to renal function following denosumab.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Observational
- Population PK Modeling of Denosumab Biosimilar MB09 and Reference Denosumab to Establish PK Similarity.Pharmaceutics · 2025Article
- Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS.Journal of bone oncology · 2025Article
- High-dose denosumab (Xgeva®) Associated Medication-Related Osteonecrosis of the Jaws (MRONJ): incidence and clinical characteristics in a retrospective analysis of 1278 patients.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Bone Metastases from Gastric Cancer Resembling Paget's Disease: A Case Report.Journal of clinical medicine · 2022Article
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Experience with denosumab (XGEVA®) for prevention of skeletal-related events in the 10 years after approval.Journal of bone oncology · 2022Review
- A Case of Recurrent Severe Hypocalcemia with Prolonged Hospitalization and Readmissions After Single Dose of Denosumab in Metastatic Prostate Cancer Patient.Journal of community hospital internal medicine perspectives · 2022Article
- Safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors.Frontiers in oncology · 2022Article
- Dynamic modeling of bone remodeling, osteolytic metastasis and PK/PD therapy: introducing variable order derivatives as a simplification technique.Journal of mathematical biology · 2021Review
- Ten-Year Simulation of the Effects of Denosumab on Bone Remodeling in Human Biopsies.JBMR plus · 2021Article
- The Efficacy of Denosumab in the Management of a Tibial Paediatric Aneurysmal Bone Cyst Compromised by Rebound Hypercalcaemia.Case reports in pediatrics · 2020Article
- Current treatment strategies for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs).Clinical diabetes and endocrinology · 2018Review
- Metformin inhibits RANKL and sensitizes cancer stem cells to denosumab.Cell cycle (Georgetown, Tex.) · 2017Article
- BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody which binds to receptor activator of nuclear factor kappa-B ligand (RANKL), for the treatment of skeletal-related events (SREs) in patients with advanced cancer and bone metastases.
methodsA total of 708 patients (116 healthy patients and 592 patients with solid tumours or multiple myeloma and bone metastases) included in seven clinical studies were evaluated for denosumab pharmacokinetics. Denosumab was administered as a single subcutaneous (s.c.) dose or multiple s.c. doses, ranging from 0.1 to 3.0 mg kg(-1) or 30 mg to 180 mg fixed dosing, every 1 or 3 months for up to 45 months.
resultsConsistent with the results in healthy adults, single s.c. doses of denosumab demonstrated dose-dependent, non-linear pharmacokinetics in advanced cancer patients with bone metastases across a wide dose range (0.1-3.0 mg kg(-1) ). Reductions in levels of the bone turnover marker, uNTx/Cr, were observed within 1 day. The duration of reductions generally increased with dose and dosing frequency. In patients with solid tumours and bone metastases, pharmacokinetics and pharmacodynamic comparisons across tumour types and concomitant cancer therapies (chemotherapies and/or hormone therapies) suggest that neither tumour type nor type of concomitant therapy markedly affects denosumab pharmacokinetics or pharmacodynamics.
conclusionsDenosumab displayed non-linear pharmacokinetics at doses below 60 mg but at higher doses, denosumab exposure increased approximately dose-proportionally in advanced cancer patients with bone metastases. Following a 120 mg, every 4 weeks dosing schedule, similar denosumab pharmacokinetics and pharmacodynamics were observed across tumour types and were independent of concomitant cancer therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.