文档介绍：Current status of EGFR-targeted cancer therapy
S, Surgery; RT, Radiotherapy; CT, Chemotherapy/hormone therapy EGFR, epidermal growth factor receptor
Pre- malignancy
Localized
tumors
Locally/ regionally
advanced disease
Advanced/
metastatic
disease
S
RT
CT + RT
CT
EGFR-targeted therapy
Potential treatment options for EGFR-targeted therapies
The concept
Targeted therapy for a broad range mon 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 es in the treatment mon solid tumors
From concept to clinical trials
Tumor
response
mAbs
TKIs
K
K
K
mAbs, monoclonal antibodies; TKIs, tyrosine kinase inhibitors
Clinical development of anticancer agents
Typical cytotoxic OBD >MTD
MTD
OBD
Toxicity
Antitumor
effect
Effect
Target
Dose
OBD
MTD
Novel targeted agents OBD <MTD
OBD, optimal biologic dose; MTD, maximum tolerated dose Rowinsky 2000
Dose
Effect
Target
Antitumor
effect
Toxicity
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