ArticleLung cancer (Amsterdam, Netherlands)2015
Dovitinib and erlotinib in patients with metastatic non-small cell lung cancer: A drug-drug interaction.
Article in Lung cancer (Amsterdam, Netherlands), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Differential induction of hepatic CYP enzymes by tobacco products and e-cigarettes: recommendation to rethink smoking status in clinical pharmacology.Archives of toxicology · 2026Article
- Inhibition of purine nucleoside and nucleobase transporters by tyrosine kinase inhibitors.PloS one · 2026Article
- Evaluating CYP enzyme induction by cigarette smoking: a new in vitro approach using primary human hepatocytes.Archives of toxicology · 2025Article
- Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.Cancer science · 2025Article
- Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.Archives of oral biology · 2023Article
- FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes.NPJ precision oncology · 2023Article
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
- A New Validated HPLC-MS/MS Method for Quantification and Pharmacokinetic Evaluation of Dovitinib, a Multi-Kinase Inhibitor, in Mouse Plasma.Drug design, development and therapy · 2020Article
- Fibroblast growth factor receptors as treatment targets in clinical oncology.Nature reviews. Clinical oncology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
introductionErlotinib is a FDA approved small molecule inhibitor of epidermal growth factor receptor and dovitinib is a novel small molecule inhibitor of fibroblast growth factor and vascular endothelial growth factor receptor. This phase 1 trial was conducted to characterize the safety and determine the maximum tolerated dose of erlotinib plus dovitinib in patients with previously treated metastatic non-small cell lung cancer.
methodsEscalating dose cohorts of daily erlotinib and dovitinib dosed 5 days on/2 days off, starting after a 2-week lead-in of erlotinib alone, were planned. A potential pharmacokinetic interaction was hypothesized as dovitinib induces CYP1A1/1A2. Only cohort 1 (150 mg erlotinib+300 mg dovitinib) and cohort -1 (150 mg erlotinib+200mg dovitinib) enrolled. Plasma concentrations of erlotinib were measured pre- and post-dovitinib exposure.
resultsTwo of three patients in cohort 1 had a DLT (grade 3 transaminitis and grade 3 syncope). Two of 6 patients in cohort -1 had a DLT (grade 3 pulmonary embolism and grade 3 fatigue); thus, the study was terminated. Erlotinib exposure (average Cmax 2308±698 ng/ml and AUC 0-24 41,030±15,577 ng×h/ml) approximated previous reports in the six patients with pharmacokinetic analysis. However, erlotinib Cmax and AUC0-24 decreased significantly by 93% (p=0.02) and 97% (p<0.01), respectively, during dovitinib co-administration.
conclusionsThis small study demonstrated considerable toxicity and a significant pharmacokinetic interaction with a marked decrease in erlotinib exposure in the presence of dovitinib, likely mediated through CYP1A1/1A2 induction. Given the toxicity and the pharmacokinetic interaction, further investigation with this drug combination will not be pursued.
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