A Phase I/II Study Combining Erlotinib andDasatinib for Non-Small Cell Lung Cancer

作者：Gold Kathryn A; Lee J Jack; Harun Nusrat; Tang Ximing; Price Justina; Kawedia Jitesh D; Tran Hai T; Erasmus Jeremy J; Blumenschein George R; William Awilliam N; Wistuba Ignacio I; Johnson Faye M^*

来源：Oncologist, 2014, 19(10): 1040-1041.

DOI：10.1634/theoncologist.2014-0228

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. %26lt;br%26gt;Methods. The phase I 313 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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusion. 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.

• 出版日期2014-10