Dual inhibition of the epidermal growth factor receptor with cetuximab, an IgG1 monoclonal antibody, and gefitinib, a tyrosine kinase inhibitor, in patients with refractory non-small cell lung cancer (NSCLC): a phase I study.

摘要: Purpose To determine the optimal doses of antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab and EGFR tyrosine kinase inhibitor gefitinib when administered as a combination for patients with advanced/metastatic non-small cell lung cancer (NSCLC) previously treated platinum-based chemotherapy. Patients Methods NSCLC prior chemotherapy received escalating weekly (100, 200, 250 mg/m 2 , IV) fixed (250 mg/d, PO) until disease progression or unacceptable toxicity. Available tumor samples were analyzed expression, gene copy number mutations, K - RAS mutations. Results Thirteen enrolled in three cohorts. Treatment was generally well-tolerated at all doses. One grade 3 headache, observed on first treatment cycle initially considered dose-limiting toxicity (DLT); this event eventually determined to be caused by brain metastasis, not Three cases 3/4 hypomagnesemia 1 case skin rash occurred highest-dose cohort. Grade 1/2 infusion reactions without requiring discontinuation. Four (31%) achieved stable disease, no responses observed. None had mutations amplification their samples. Conclusion Dual inhibition is feasible; can safely may have modest activity NSCLC. Cetuximab IV mg/d PO recommended phase II dose, although potential late-onset warrants close monitoring receiving combined dosage.