ArticleInvestigational new drugs2012
Phase I and pharmacokinetic study of dasatinib and cetuximab in patients with advanced solid malignancies.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.Journal of the American Heart Association · 2017Pooled it
- Final report on North Central Cancer Treatment Group N0877 (alliance): A phase II randomized, placebo-controlled trial of chemoradiotherapy with or without dasatinib for glioblastoma.Neuro-oncology · 2025Trial
- Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer.JCI insight · 2017Trial
- Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck.Annals of oncology : official journal of the European Society for Medical Oncology · 2013Trial
- Article
- Neurotoxicity of Tumor Immunotherapy: The Emergence of Clinical Attention.Journal of oncology · 2022Review
- Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2021Review
- Identification of a Triple Drug Combination That Is Synergistically Cytotoxic for Triple-Negative Breast Cancer Cells Using a Novel Combination Discovery Approach.SLAS discovery : advancing life sciences R & D · 2020Article
- Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib.Clinical pharmacokinetics · 2020Review
- Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far.Cancers · 2020Review
- A phase I study of gemcitabine + dasatinib (gd) or gemcitabine + dasatinib + cetuximab (GDC) in refractory solid tumors.Cancer chemotherapy and pharmacology · 2019Article
- QT Interval Prolongation Associated With Cytotoxic and Targeted Cancer Therapeutics.Current treatment options in oncology · 2019Review
- IL6 is associated with response to dasatinib and cetuximab: Phase II clinical trial with mechanistic correlatives in cetuximab-resistant head and neck cancer.Oral oncology · 2017Article
- Degradation of epidermal growth factor receptor mediates dasatinib-induced apoptosis in head and neck squamous cell carcinoma cells.Neoplasia (New York, N.Y.) · 2012Article
- Anaphylactic reactions to oligosaccharides in red meat: a syndrome in evolution.Clinical and molecular allergy : CMA · 2012Article
- Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors.Cancer treatment reviews · 2010Review
- Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors.Journal of oncology · 2009Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundCombined inhibition of epidermal growth factor receptor (EGFR) and Src family kinases (SFK) may lead to improved therapeutic effects. We evaluated the combination of dasatinib, an inhibitor of SFK and other kinases, and cetuximab, an anti-EGFR monoclonal antibody. PATIENTS AND
methodsPatients with advanced solid malignancies received cetuximab intravenously on a standard weekly schedule and dasatinib orally, once daily at 3 dose levels: (1) 100 mg, (2) 150 mg, (3) 200 mg. Pharmacokinetic and pharmacodynamic studies of dasatinib were performed prior to starting cetuximab and following 14 days of treatment.
resultsTwenty-five patients (3 dose level 1; 19 dose level 2; 3 dose level 3) were initially treated. Three patients developed dose-limiting toxicities: 1 at dose level 2 (headache) and 2 at dose level 3 (headache, nausea). Grade 3-4 toxicities in more than 2 patients included: dyspnea (4), vomiting (4), nausea (3), hypersensitivity reactions (3), headache (3) and anemia (3). Twenty-one patients developed headache (8 grade 1; 10 grade 2), which occurred after the loading of cetuximab and lasted 1-3 days. Six additional patients were treated with dasatinib starting 3 days after the loading dose of cetuximab; none developed headache after dasatinib. Dasatinib pharmacokinetics and a transient decrease in SFK PY416 levels in peripheral blood mononuclear cells were not altered by cetuximab. Patients with higher plasma TGF-alpha levels had worse progression-free survival.
conclusionsDasatinib 150 mg once daily plus weekly cetuximab is recommended for phase II studies. Early-onset headache was ameliorated by starting dasatinib after cetuximab.
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