EGFR靶向治疗癌症.pptVIP

Current status of EGFR-targeted cancer therapy Potential treatment options for EGFR-targeted therapies From concept to clinical trials Clinical development of anticancer agents Clinical development of EGFR-targeted therapies Phase I trials failed to identify the MTD of cetuximab; the OBD was identified as the dose that saturated the antibody systemic clearance rate (200 mg/m2/week) Gefitinib (IRESSA) Phase I trials did identify the MTD (700-1000 mg/day), but also showed that the OBD was 250 mg/day, as confirmed in Phase II trials Phase I trials of erlotinib identified the MTD as 150 mg/day; this is the recommended dose Cetuximab: approved for the treatment of advanced colorectal cancer Gefitinib (250 mg/day): approved for the treatment of advanced NSCLC Erlotinib: awaiting approval for the treatment of advanced NSCLC Other EGFR-targeted therapies under clinical development Summary of current EGFR-targeted treatment options To date, two EGFR-targeted therapies have been approved for the treatment of patients with advanced or metastatic CRC (cetuximab) or NSCLC (gefitinib) Approval of erlotinib for the treatment of advanced NSCLC is expected in 2004 Several other EGFR-targeted therapies are undergoing clinical development, with the majority showing some activity in a range of solid tumors S, Surgery; RT, Radiotherapy;CT, Chemotherapy/hormone therapyEGFR, epidermal growth factor receptor Pre-malignancy Localized tumors Locally/ regionally advanced disease Advanced/ metastatic disease S RT CT + RT CT EGFR-targeted therapy The concept Targeted therapy for a broad range of common solid tumors (including lung, breast, prostate, colon, ovarian, and gastric) Clinical trials Proof of concept well-tolerated therapy tumor responses in several tumor types The potential Improved outcomes in the treatment of common solid tumors Tumor response mAbs TKIs K K K mAbs, monoclonal antibodies; TKIs, tyrosine kinase inhibitors Typical cytotoxicOBD MTD MTD OBD Toxi