title: A phase I/II study combining erlotinib and dasatinib for non-small cell lung cancer.
abstract: BACKGROUND
  EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC.
  
  
  METHODS
  The phase I 3+3 dose-escalation study enrolled patients with solid tumors to determine the MTD. The phase II trial enrolled patients with advanced NSCLC who had undergone no previous treatments to determine progression-free survival (PFS) and response. Pharmacokinetic and tissue biomarker analyses were performed.
  
  
  RESULTS
  MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion. No responses were observed in phase I. The 35 NSCLC patients treated in phase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. Median PFS was 3.3 months. Epithelial-mesenchymal transition markers did not correlate with outcomes.
  
  
  CONCLUSIONS
  The combination of erlotinib and dasatinib is safe and feasible in NSCLC. The results of this study do not support use of this combination in molecularly unselected NSCLC.
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Gold
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Harun
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Justina
authors.initials: J
authors.lastname: Price
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Jitesh D
authors.initials: JD
authors.lastname: Kawedia
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Erasmus
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA;
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas, USA; fmjohns@mdanderson.org.
authors.forename: Faye M
authors.initials: FM
authors.lastname: Johnson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000069439:Dasatinib / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D014408:Biomarkers, Tumor; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D000069439:Dasatinib