Perspectives on salvage therapy for non-small-cell lung cancer

Platinum-based chemotherapy offers a modest survival advantage over best supportive care in chemotherapy-naive patients with a good performance status 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 clinicalpractice, an increasing number of patients maintain a good performance status after first-line treatment and are eligible for further treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every 3 weeks has been the standard of care for second-line chemotherapy since the year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolate agent with single-agent activity in first- and second-line treatment of NSCLC. A large phase 111 study comparing docetaxel to pemetrexed in second-line therapy demonstrated that pemetrexed is equally active and less toxic than docetaxel. Based on these results, pemetrexed is a reasonable second-line chemotherapy option for patients with recurrent, advanced NSCLC. Progress made in the field of molecular biology has led to the identification of drugs active against specific cellular targets. Gefitinib (Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitors of the epidermal growth factor receptor. Phase II and III trials have demonstrated that these agents are active particularly in a subgroup of patients with specific biologic characteristics. Both drugs have been approved for the treatment of pretreated NSCLC. Other drugs, such as cetuximab (Erbitux) and bevacizumab (Avastin) have shown promising activity in NSCLC and are currently being tested in clinical trials.