Clin Cancer Res
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Epidermal growth factor receptor (EGFR), a protein tyrosine kinase expressed in many types of human cancers, has been strongly associated with tumor progression. Cetuximab is an IgG(1) anti-EGFR chimeric mouse/human monoclonal antibody that has been approved for the treatment of advanced colon cancer. Using human tumor xenografts grown in nude mice, we have determined the in vivo pharmacodynamic response of cetuximab at efficacious doses. Three pharmacodynamic end points were evaluated: tumoral phospho-EGFR, tumoral mitogen-activated protein kinase (MAPK) phosphorylation, and Ki67 expression. ⋯ Phospho-EGFR/phospho-MAPK could be useful clinical biomarkers to assess EGFR inhibition by cetuximab.
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Irinotecan and cisplatin (IP) significantly improved survival compared with etoposide and cisplatin (EP), in patients with extensive-stage small cell lung cancer (SCLC) in a previous Japan Clinical Oncology Group (JCOG) randomized trial. JCOG9903 was conducted to evaluate the safety of sequentially given IP following concurrent EP plus twice-daily thoracic irradiation (TRT) for the treatment of limited-stage SCLC (LSCLC). ⋯ IP following concurrent EP plus twice-daily TRT is safe with acceptable toxicities. A randomized phase III trial comparing EP with IP following EP plus concurrent TRT for LSCLC is ongoing (JCOG0202).