Gemcitabine for the treatment of advanced nonsmall cell lung cancer

Gemcitabine is a pyrimidine nucleoside antimetabolite agent which is active in several human malignancies, including nonsmall cell lung cancer (NSCLC). Because of its acceptable toxicity profile, with myelosuppression being the most common adverse event, gemcitabine can be safely combined with a number of cytotoxic agents, including platinum derivatives and new-generation anticancer compounds. In fact, the combination of gemcitabine and cisplatin is a first-line treatment for patients with advanced NSCLC, pharmacoeconomic data indicating that it represents the most cost-effective regimen among platinum-based combinations with third-generation cytotoxic drugs. The drug has been investigated in the context of nonplatinum-based regimens in a number of prospective clinical trials, and might provide a suitable alternative for patients with contraindications to platinum. Recently, gemcitabine-based doublets have been successfully tested in association with novel targeted agents with encouraging results, providing further evidence for the role of the drug in the treatment of NSCLC. In the last few years several attempts have been pursued in order to identify molecular predictors of gemcitabine activity, and recent data support the feasibility of genomic-based approaches to customize treatment with the ultimate goal of improving patient outcome.