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How Today’s Developments in the Treatment of Non-Small Cell Lung Cancer Will Change Tomorrow’s Standards of Care

Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Key Words. NSCLC • EGFR • Adjuvant • Neoadjuvant • Docetaxel • Gefitinib • Bevacizumab • Erlotinib

Correspondence: Mark G. Kris, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. Telephone: 212-639-7590; Fax: 212-794-4357.

Cisplatin (Platinol^®; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin^®; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere^®; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol^®; Bristol-Myers Squibb), vinorelbine (Navelbine^®; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta^®; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar^®; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin^®; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB–IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa^®; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva^®; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) in operable NSCLC are planned. One such study includes cisplatin and docetaxel. Effective development of active agents and disease management based on molecular profiling of lung tumors will change tomorrow’s standard of care.

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