Silvia Novello, MD

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.

The prognosis of patients with advanced non–small-cell lung cancer(NSCLC) remains poor. Systemic chemotherapy prolongs survivalin this group of patients and palliates symptoms compared to bestsupportive care alone but more effective therapeutic strategies areneeded. Novel agents that selectively target biological pathways oftumor growth offer hope of improving response and survival ratesbeyond what has been achieved with standard cytotoxic chemotherapy.Part 2 of this two-part article addresses the role of chemotherapy inlocally advanced and advanced NSCLC, including the use of novelagents, considerations in elderly patients, and studies of second-linetreatment.

Non–small-cell lung cancer (NSCLC) accounts for approximately80% of all lung tumors. Patients diagnosed with early-stage diseasegenerally undergo surgery, but up to 50% develop local or distantrecurrences. The benefit of chemotherapy in this disease is modest, butnew drugs and combined strategies offer hope of improved survivalrates. Because the disease recurs outside the chest in 70% of cases, oneof the foremost goals of therapy is to prevent distant dissemination. Tothis end, chemotherapy may be administered preoperatively or afterresection of the tumor. The first part of this article, which concludesnext month, will address adjuvant and neoadjuvant chemotherapy inearly-stage non–small-cell lung cancer.