Title: Intercalation of Erlotinib and Pemetrexed in the Treatment of Non-Small Cell Lung Cancer
VOLUME: 11 ISSUE: 1
Author(s):Tianhong Li, Primo N. Lara Jr., Philip C. Mack, Roman Perez-Soler, David R. Gandara, Gert van Assche, Severine Vermeire and Paul Rutgeerts
Affiliation:University of California Davis Cancer Center, Division of Hematology&Oncology, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA., Department of Gastroenterology, Leuven University Hospitals, 49 Herestraat, Leuven, Belgium.
Keywords:Pemetrexed, multi-targeted antifolate, erlotinib, small molecule tyrosine kinase inhibitor (TKI), epidermal growth factor receptor (EGFR), non-small cell lung cancer (NSCLC), Mucosal healing, endoscopy, medical therapy, IBD, Crohn's disease, ulcerative colitis
Abstract: Both the multi-targeted antifolate pemetrexed and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib have established roles in the treatment of advanced non-small cell lung cancer (NSCLC). Given different mechanisms of action and minimal overlapping toxicities, combinations of these agents have been considered. However, four previous phase III trials investigating concurrent chemotherapy with or without EGFR TKIs showed no clinical benefit. Based on preclinical data, we developed a model of pharmacodynamic separation to avoid potential negative interactions between chemotherapy and EGFR TKIs in NSCLC tumors containing wild-type EGFR gene. This review summarizes the background, scientific rationale and early clinical data in support of intercalation of intermittent erlotinib dosing with pemetrexed as a means of achieving pharmacodynamic separation. Ongoing research efforts investigating this concept are reviewed.
