Giorgio V. Scagliotti, MD, PhD

Since the publication of a meta-analysis in 1995 that demonstrated a modest survival benefit compared to best supportive care, platinum-based chemotherapy became the cornerstone of therapy in the first-line setting in advanced-stage non–small-cell lung cancer (NSCLC) for patients with good performance status.[1] A recent meta-analysis of 16 randomized trials including 2,714 patients demonstrated an advantage of chemotherapy over best supportive care with an absolute improvement in survival of 9% at 12 months.[2]

Pemetrexed (Alimta) possesses broad antitumor activity. It has beenevaluated in non–small-cell lung cancer (NSCLC) as front-line chemotherapyin a comprehensive phase II evaluation. While variousantifolates have been previously evaluated in clinical trials, drug developmentwas stopped or delayed in light of their lack of efficacy oroccurrence of life-threatening toxicities. While similar trends were observedwith pemetrexed early in development, investigators institutedfolic acid and vitamin B12 supplementation to minimize these toxicitieswithout hampering drug efficacy. This article briefly summarizes thecurrent evidence that supports the role of pemetrexed-based combinationsin clinical trials for chemonaive patients with advanced NSCLC.

A total of 332 patients with advanced non-small-cell lung cancer were randomized by the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative