Clinical Responses to EGFr-TKI’s characterized by drug-induced cell death in human NSCLC primary cultures

18184 Background: Small molecule inhibitors of the EGFr have proven effective in advanced NSCLC but response rates in unselected populations remain low. Certain subsets of patients appear favored including females, non-smokers and Asians. Molecular profiles suggest that gene amplification or EGFr mutations (codons 19–21) may underlie responses. Our prior observations (Proc. AACR 2002, Abs.3902) indicated that gefitinib and erlotinib induced cell-death in human tumor microspheroids isolated from surgical specimens of some NSCLC patients, suggesting programmed cell death to be an important mechanism of action for these molecules. As part of an IRB-approved clinical trial, patients whose tumors were found sensitive to the EGFr-TKI’s by laboratory analysis, received 1st line single agent oral erlotinib at 150 mg/day. Methods: Following informed consent, NSCLC patients participating in the trial provided tissue for analysis as previously described (J Clin Oncol, 2000 18: 2245–2249). Dose response curves provid...