First-line treatment of non small cell lung cancer

Combination of two drugs including cisplatin represents the standard first line treatment for fit patients with advanced non-small cell lung cancer. This therapy has shown to produce a modest but statistically significant increase in patient survival when compared with best supportive care alone. New cytotoxic agents have been introduced in clinical practice in the last decade. These drugs, including pemetrexed, gemcitabine, vinorelbine and taxanes, have produced further survival improvements over old-generation regimens. Comparison studies aimed at identifying the best cytotoxic regimen have shown similar activity between new drug combinations, with differences only in toxicity and costs. Two-drug regimens have been found to be more active than single-agent chemotherapy, while comparison studies with three-drug combinations have shown that the latter have the same efficacy but increased toxicity and costs, and therefore their use is not recommended in clinical practice. To reduce the risks associated with cisplatin administration new platinum analogues, as carboplatin, and new generation non-platinum containing regimens have been assessed. These combinations produced comparable outcome in terms of survival with platinum-based regimens and can represent an alternative for those patients with major contraindications to cisplatin. Single agent chemotherapy represents the standard first-line treatment for elderly patients with advanced disease, although platinum combinations can be considered in selected cases. Recent data indicate that specific targeted agents as bevacizumab or cetuximab can further improve outcome in clinically or biologically selected cohorts of patients when administered with chemotherapy over chemotherapy alone. Additional improvements can be obtained with pharmacogenomics. Customizing treatments based on biological tumor profiling will allow to identify and treat with a specific drug only patients with potential sensitivity features, optimizing tumor response and sparing useless adverse events to resistant subjects.