Giulio Metro, MD

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Perspectives on Salvage Therapy for Non–Small-Cell Lung Cancer

July 1st 2005

Platinum-based chemotherapy offers a modest survival advantage overbest supportive care in chemotherapy-naive patients with a good performancestatus and advanced/metastatic non–small-cell lung cancer(NSCLC). Despite the survival benefit associated with first-line chemotherapy,the majority of patients will experience relapse or disease progression.In clinical practice, an increasing number of patients maintaina good performance status after first-line treatment and are eligible forfurther treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every3 weeks has been the standard of care for second-line chemotherapy sincethe year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolateagent with single-agent activity in first- and second-line treatment ofNSCLC. A large phase III study comparing docetaxel to pemetrexed insecond-line therapy demonstrated that pemetrexed is equally active andless toxic than docetaxel. Based on these results, pemetrexed is a reasonablesecond-line chemotherapy option for patients with recurrent, advancedNSCLC. Progress made in the field of molecular biology has led to theidentification of drugs active against specific cellular targets. Gefitinib(Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitorsof the epidermal growth factor receptor. Phase II and III trialshave demonstrated that these agents are active particularly in a subgroupof patients with specific biologic characteristics. Both drugs have beenapproved for the treatment of pretreated NSCLC. Other drugs, such ascetuximab (Erbitux) and bevacizumab (Avastin) have shown promisingactivity in NSCLC and are currently being tested in clinical trials.