The Effects of Cetuximab Alone and in Combination With Radiation and/or Chemotherapy in Lung Cancer

摘要: Purpose: The epidermal growth factor receptor (EGFR) overexpressed in approximately 80% of non-small cell lung cancers (NSCLC) is a target for novel therapeutics. Concurrent chemoradiation the current standard care treatment patients with locally advanced NSCLC. However, vitro and vivo . Experimental Design: We evaluated EGFR status panel human NSCLC cancer lines by immunohistochemistry flow cytometry. then cetuximab effects on growth, cycle distribution, downstream intracellular signaling molecules this lines. were treated alone or combination radiation, chemotherapy, to determine cooperative both athymic nude mice bearing xenografts. Results: Cetuximab inhibited some but not all EGFR-expressing dose-dependent manner. Flow cytometric analysis distribution after 24 hours revealed shift into G 0 /G 1 phase cetuximab-sensitive at concentrations that growth-inhibitory. There no changes EGFR-negative After 4 exposure, reduced (EGF)-induced phosphorylation (pEGFR) HER-2 (pHER2) cetuximab-resistant EGF-induced extracellular signal-regulated kinase-1/2 (pERK) In absence EGF, increased level pEGFR pHER2 above seen untreated control cells sensitive resistant EGFR- HER2-positive, HER2-negative Despite cetuximab-induced increase HER2, peak levels Cooperative (combination index values assays radiation only A lack cooperation was cetuximab-insensitive Similar findings observed studies plus cisplatin paclitaxel. EGFR-expressing, cetuximab-sensitive, line xenografts, induced marked improvement tumor inhibition over either agent alone. inhibitory cetuximab-radiation similar concurrent chemoradiation. Triple therapy yielded nonsignificant advantage doublet combinations (cetuximab chemoradiation) Conclusions: results cisplatin-radiation provide rationale clinical investigation selected Local toxicity should be between regimens. Proper patient selection will critical success such trials further are needed identify optimal criteria.