非小细胞肺癌的靶治疗.pptVIP

Targeted Therapy in Non-Small-Cell Lung Cancer 非小細胞肺癌的標靶治療 NSCLC- Survival by Stage NSCLC Treatment The “First Generation” Agents Methotrexate, cyclophosphamide, vincristine, and doxorubicin—were essentially inactive in NSCLC, despite being widely used in the 1970s and 1980s. The “2nd Generation” Agents Cisplatin, ifosfamide, mitomycin, vindesine, vinblastine, and etoposide in late 1980. The “3rd Generation” Agents Paclitaxel, docetaxel, gemcitabine and vinorelbine emerged in the chemotherapy of NSCLC In the middle 1990s. Cisplatin-based doublets are the mainstay of chemotherapy for advanced NSCLC. The “4th Generation” Agents Targeted therapy in early 2000s. Target Validation The target should be present and functionally abnormal relative to normal tissue. The target should influence tumor biology manifested through differences in pt outcome. Interfering with target function in model systems should alter tumor biology. Interfering with the target in the clinics should alter pt survival or reverse clinical symptoms associated with the cancer under treatment. Epidermal Growth Factor Receptor Inhibition (EGFRI) Inhibition of the EGFR signaling pathway Tyrosine kinase inhibitors (TKIs) IDEAL 1 2: design schema Prognostic Factors Associated with an Objective Response Adenocarcinoma non-Adeno Female male Japanese non-Japanese BAC Non-smoker IDEAL 1: drug-related toxicities by dose IDEAL 2: drug-related toxicities by dose Accelerated approval regulations FDA allow pharmaceutical manufacturers to offer pts treatment for life-threatening diseases. This may occur when early evidence suggests that the agent is likely to improve survival or reduce symptoms, before confirmatory studies are safe and efficacious. Iressa was marketed in May, 2003 in U.S.A. AZ need another phase III trial. Acute Interstitial Pneumonitis Iressa was approved in Japan in July, 2002. From August to December, 19000 pts received iressa (1) 358 (1.9%) pts developed interstitial