Pemetrexed plus carboplatin or oxaliplatin in advanced non-small cell lung cancer

Over the past decade many large randomized trials have been conducted in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC); however, no single regimen has shown clear superiority. Typical response rates of 17% to 32%, median survival times of 7 to 10 months, and 1-year survival rates of 30% to 45% are common in such studies. Nevertheless, metastatic NSCLC remains an incurable disease, with the development of drug resistance as a major impediment. New treatment regimens, such as the broadly used antifolate antimetabolites, target multiple metabolic functions and may lead to improvements in clinical outcome. Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a novel antifolate, distinguished by a unique nuclear structure and its ability to inhibit multiple folate-dependent enzymatic pathways. Typically, vitamin B12 and folic acid supplementation are incorporated into the treatment regimen to ameliorate untoward toxicities. When used either as a single agent or in combination with cis-diamine platinums (eg, cisplatin, carboplatin) or diaminocyclohexane platinums (eg, oxaliplatin), pemetrexed has shown significant antitumor activity, with mild, manageable toxicity in patients with advanced NSCLC.