ArticleCancer chemotherapy and pharmacology2012
Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients.
Article in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.International journal of molecular sciences · 2024Pooled it
- Exosome-based strategies for diagnosis and therapy of glioma cancer.Cancer cell international · 2022Review
- Anti-angiogenic therapies in the management of glioblastoma.Chinese clinical oncology · 2021Article
- Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Medulloblastoma drugs in development: Current leads, trials and drawbacks.European journal of medicinal chemistry · 2021Review
- Therapeutic strategies of recurrent glioblastoma and its molecular pathways 'Lock up the beast'.Ecancermedicalscience · 2021Review
- Nanodelivery Systems Targeting Epidermal Growth Factor Receptors for Glioma Management.Pharmaceutics · 2020Review
- Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches.Contemporary oncology (Poznan, Poland) · 2020Review
- The oncogenic roles of 27-hydroxycholesterol in glioblastoma.Oncology letters · 2019Article
- Identification of Potent VEGF Inhibitors for the Clinical Treatment of Glioblastoma, A Virtual Screening Approach.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Brain Distribution of a Panel of Epidermal Growth Factor Receptor Inhibitors Using Cassette Dosing in Wild-Type andDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- Receptor tyrosine kinase-Ras-PI 3 kinase-Akt signaling network in glioblastoma multiforme.Medical oncology (Northwood, London, England) · 2018Review
- Quantitative perfusion imaging of neoplastic liver lesions: A multi-institution study.Scientific reports · 2018Article
- Antibody-drug conjugates in glioblastoma therapy: the right drugs to the right cells.Nature reviews. Clinical oncology · 2017Review
- Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.Journal of cancer research and clinical oncology · 2016Review
- Lessons from anti-vascular endothelial growth factor and anti-vascular endothelial growth factor receptor trials in patients with glioblastoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Article
- Circulating glioma biomarkers.Neuro-oncology · 2015Review
- The challenges and the promise of molecular targeted therapy in malignant gliomas.Neoplasia (New York, N.Y.) · 2015Review
- Antiangiogenic therapy for glioblastoma: current status and future prospects.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
- Targeted molecular therapies against epidermal growth factor receptor: past experiences and challenges.Neuro-oncology · 2014Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
purposeVascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) play a significant role in glioblastoma angiogenesis and proliferation, making tyrosine kinase (TK) receptors logical targets for treatment. We evaluated AEE788, a reversible TK inhibitor that inhibits EGFR and VEGFR, in recurrent glioblastoma patients.
methodsIn this dose-escalation, phase I study, patients with recurrent glioblastoma received AEE788 once daily in 28-day cycles in stratified subgroups: those receiving (1) non-enzyme-inducing anticonvulsants drugs or no anticonvulsants (Group A) and (2) enzyme-inducing anticonvulsant drugs (Group B). A dose-expansion phase stratified patients by surgical eligibility. Primary objectives were to determine dose-limiting toxicity (DLT) and maximum tolerated dose; secondary objectives included evaluating (1) safety/tolerability, (2) pharmacokinetics, and (3) preliminary antitumor activity.
resultsSixty-four glioblastoma patients were enrolled. Two Group A patients experienced DLTs (proteinuria and stomatitis) at 550 mg; 550 mg was, therefore, the highest dose evaluated and dose limiting. One Group B patient receiving 800 mg experienced a DLT (diarrhea). The initially recommended dose for dose-expansion phase for Group A was 400 mg; additional patients received 250 mg to assess the hepatotoxicity. Most frequently reported adverse events (AEs) included diarrhea and rash. Serious AEs, most commonly grade 3/4 liver function test elevations, were responsible for treatment discontinuation in 17% of patients. AEE788 concentrations were reduced by EIACD. The best overall response was stable disease (17%).
conclusionsContinuous, once-daily AEE788 was associated with unacceptable toxicity and minimal activity for the treatment of recurrent glioblastoma. The study was, therefore, discontinued prematurely.
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Registered trials
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.