Intercalation of erlotinib and pemetrexed in the treatment of non-small cell lung cancer

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalCurrent Drug Targets
Volume11
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Epidermal growth factor receptor (EGFR)
  • Erlotinib
  • Multi-targeted antifolate
  • Non-small cell lung cancer (NSCLC)
  • Pemetrexed
  • Small molecule tyrosine kinase inhibitor (TKI)

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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