INTRODUCTION: Erlotinib 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.
METHODS: Escalating 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.
RESULTS: Two 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.
CONCLUSIONS: This 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.