ArticleInvestigational new drugs2007
Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC).
Article in Investigational new drugs, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma.Investigational new drugs · 2016Trial
- A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients.Investigational new drugs · 2014Trial
- Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer.BJU international · 2013Trial
- Multitargeted tyrosine kinase inhibition produces discordant changes between 99mTc-MDP bone scans and other disease biomarkers: analysis of a phase II study of sunitinib for metastatic castration-resistant prostate cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2012Trial
- Cediranib (AZD2171) in patients with advanced hepatocellular carcinoma: a phase II North Central Cancer Treatment Group Clinical Trial.American journal of clinical oncology · 2012Trial
- Cancer-Associated Fibroblasts in Prostate Cancer: Unraveling Mechanisms and Therapeutic Implications.Oncology research · 2026Review
- Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.Molecular cancer · 2024Review
- Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies.Investigational new drugs · 2022Article
- Population exposure-safety analysis of cediranib for Phase I and II studies in patients with cancer.British journal of clinical pharmacology · 2018Article
- Population pharmacokinetic and exposure simulation analysis for cediranib (AZD2171) in pooled Phase I/II studies in patients with cancer.British journal of clinical pharmacology · 2017Article
- Clinical Pharmacokinetics and Pharmacodynamics of Cediranib.Clinical pharmacokinetics · 2017Review
- Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?Targeted oncology · 2016Review
- Pharmacokinetic Aspects of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors.Clinical pharmacokinetics · 2016Review
- A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2015Article
- Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers.Journal of bone oncology · 2015Review
- HORIZON I: Is there a future for oral anti-angiogenics on the horizon of colorectal cancer therapy?British journal of cancer · 2013Article
- Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours.Investigational new drugs · 2012Article
- Cediranib inhibits both the intraosseous growth of PDGF D-positive prostate cancer cells and the associated bone reaction.The Prostate · 2012Article
- Targeting angiogenesis for the treatment of prostate cancer.Expert opinion on therapeutic targets · 2012Review
- Small-molecule protein tyrosine kinase inhibitors for the treatment of metastatic prostate cancer.Future medicinal chemistry · 2012Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To explore the pharmacokinetics and tolerability of AZD2171, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with hormone refractory prostate cancer. Twenty-six patients received oral daily dosing of AZD2171 at 1, 2.5, 5, 10, 20, 30 mg. The maximum tolerated dose (MTD) was defined as the dose below that at which >or=33% of patients experienced a dose-limiting toxicity (DLT) within 21 days of initiating therapy. Pharmacokinetic analysis was performed. DLTs occurred at the 30 mg dose and included grade 3 events in three patients: fatigue (n = 3) and muscle weakness (n = 2). The pharmacokinetic profile revealed an effective half-life of approximately 27 h. At steady state, the unbound drug concentration was 4.4 times above the concentration required to inhibit endothelial cell proliferation in vitro. Four patients experienced PSA reductions within 30 days following drug discontinuation (one on 2.5 mg, two on 20 mg and 1 on 30 mg). In two patients treated with 20 mg, post therapy PSA declines persisted for >17 months, despite a PSA increase on therapy. Resolution of adenopathy occurred in one patient persisting for >17 months. Plasma concentrations were maximum 2-8 h post dosing with an overall median value of 2 h. The dose of 20 mg daily was declared as the MTD. One objective response and several PSA declines following the discontinuation of therapy for toxicity suggest that evidence of clinical efficacy may be delayed. While further study is indicated, careful attention must be paid to the novel toxicities of this agent with prolonged dosing.
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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.