Phase I/II trial of gefitinib and RAD001 (everolimus) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

摘要: 7104 Background: The mechanisms of resistance to EGFR tyrosine kinase inhibitors remain poorly understood but may be related, in part, dysregulation downstream apoptotic pathways, such as the PI3K/Akt/PTEN axis. In preclinical models, inhibition PI3K/Akt pathway restores gefitinib (Iressa™) sensitivity resistant cell lines. mTOR is a serine/threonine located Akt that regulates cellular growth and G1/S cycle progression. RAD001 an orally available inhibitor inhibits cancer lines, including A549. We undertook this phase I/II study characterize safety, pharmacokinetics (PK), antitumor activity combination pts with advanced NSCLC no prior history EGFR-directed therapy. Methods: Phase I: 3-pt cohorts intrapatient escalation, at dose levels 5 10 mg daily. All received 250 PK studies were performed over 3-week period during which a...