Gefitinib With or Without Simvastatin in Non-Small Cell Lung Cancer (NSCLC)
Status:
Completed
Trial end date:
2011-03-01
Target enrollment:
Participant gender:
Summary
The epidermal growth factor receptor (EGFR) is a key regulator of growth, differentiation,
and survival of epithelial cancers. In a small subset of tumors, the presence of activating
mutations within the ATP binding site confers increased susceptibility to gefitinib, a potent
tyrosine kinase inhibitor of EGFR. Agents that can inhibit EGFR function through different
mechanisms may enhance gefitinib activity in patients lacking these mutations. Mevalonate
metabolites play significant roles in the function of the EGFR; therefore, mevalonate pathway
inhibitors may potentiate EGFR-targeted therapies. Targeting HMG-CoA reductase, the
rate-limiting enzyme of mevalonate pathway, using lovastatin induces a potent apoptosis in a
variety of tumor types. In an in vitro study, combining gefitinib and lovastatin treatment
showed synergistic cytotoxic activity through enhanced inhibition of AKT activation by EGF in
NSCLC and head & neck cancer cell lines. Therefore, the investigators would like to compare
the combination effect of gefitinib and simvastatin, the specific and protein inhibitor of
HMG-CoA reductase, with gefitinib alone in previously treated patients with NSCLC.