Intercalation of Erlotinib and Pemetrexed in the Treatment of Non-Small Cell Lung Cancer

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:

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.

Cite this article as:

Li Tianhong, Lara Jr. N. Primo, Mack C. Philip, Perez-Soler Roman, Gandara R. David, Assche van Gert, Vermeire Severine and Rutgeerts Paul, Intercalation of Erlotinib and Pemetrexed in the Treatment of Non-Small Cell Lung Cancer, Current Drug Targets 2010; 11 (1) . https://dx.doi.org/10.2174/138945010790030983