Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib.

摘要: Introduction: Dual inhibition of SRC - and EGFR -dependent pathways may overcome acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients with lung adenocarcinoma mutations. The inhibitor dasatinib demonstrates antitumor activity in gefitinib-resistant cells lines xenografts. Dasatinib is tolerable advanced non-small cell cancer, combination erlotinib. Methods: We conducted this phase II study 70 mg twice daily -mutant EGFR-TKIs. After a protocol amendment based on evolving data about both drugs, received at dose 100 continued erlotinib after developing resistance. Enrolled either harbored an activating mutation or experienced clinical benefit single-agent gefitinib, followed by RECIST documented progression while being treated EGFR-TKI. Results: Twenty-one were enrolled, 9 under the original trial design 12 amendments. observed no complete partial responses (0% rate, 95% confidence interval: 0–18%). median time was 0.5 months (range, 0.2–1.8 months) 0.9 0.4–5 combination. Pleural effusions dyspnea frequent toxicities. Conclusions: has gefitinib.