Tumor growth inhibition with cetuximab and chemotherapy in non-small cell lung cancer xenografts expressing wild-type and mutated epidermal growth factor receptor.

摘要: Purpose: Targeting the epidermal growth factor receptor (EGFR) is a validated approach to treat cancer. In non–small cell lung cancer (NSCLC), EGFR contains somatic mutations in 10% of patients, which correlates with increased response rates small molecule inhibitors EGFR. We analyzed effects monoclonal IgG1 antibody Erbitux (cetuximab) NSCLC xenografts wild-type (wt) or mutated Experimental Design: lines were grown s.c. nude mice. Dose-dependent efficacy was established for cetuximab. To determine whether combination therapy produces tumor regressions, cetuximab dosed at half-maximal chemotherapy used maximum tolerated dose. Results: Cetuximab showed antitumor activity wt (A549, NCI-H358, NCI-H292) and [HCC-827 (delE746-A750), NCI-H1975 (L858R, T790M)] EGFR-expressing xenografts. H292 model, docetaxel more potent inhibit than alone. Cisplatin augmented produce 6 10 whereas 1 regressions found no regression cisplatin. Using H1975 xenografts, gemcitabine resulting 12 regressions. Docetaxel efficacious seven nine compared single treatments. inhibited autophosphorylation both lysates. Exploring underlying mechanism xenograft added antiproliferative but main component this drug induce apoptosis. Conclusions: models expressing Combination treatments cetuximab, may be important management patients chemorefractory NSCLC.