Second-line chemotherapy for non-small cell lung cancer.

Despite being considered a standard of care, administration of second-line chemotherapy for non-small cell lung cancer is limited to patients in good performance status (ECOG PS 0-1) and to selected patients with PS 2. Drugs currently approved by FDA in this setting are docetaxel, gefitinib, erlotinib and pemetrexed, while in Europe those registered with this indication are only docetaxel and pemetrexed. This short review will focus on the role of pemetrexed, from the controlled phase II trial, to the development of the vitamin supplementation strategy to decrease toxicity, to the large phase III registration trial undertaken vs. the standard docetaxel. Moreover, the huge patient material collected during this latter trial has lead to further analyses to clarify several aspects of second-line treatment, from toxicity to quality of life assessment, to its role in elderly patients and to the direct translation in terms of costs. Finally, we will give a brief overview on current trials, that mainly explore the possibility to raise pemetrexed dose, and thus to increase its activity while maintaining an acceptable toxicity.