Pemetrexed as indispensable drug for the treatment of non- squamous non-small cell lung cancer: the role in induction and maintenance therapy

Pemetrexed is a multi-targeting antifolate cytotoxic drug and, within the last decade, has brought a new paradigm shift in treatment strategies for non-squamous non-small cell lung cancer (NSCLC). In the United States, pemetrexed has been approved three times by the Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic non-squamous NSCLC in 2004, 2008 and 2009. Indications were the use as a single agent for patients in whom any prior chemotherapy has failed, the use in combination with cisplatin for the first-line treatment and the use in maintenance treatment after platinum-doublet induction chemotherapy, respectively. Owing to the advantage of less cumulative toxicities, pemetrexed has become indispensable for switchor continuation-maintenance therapy. These maintenance methods have superseded the conventional methods of the defined cycles of chemotherapy followed by drug holidays in the front-line chemotherapy. A recent topic is a challenge of further addition of any tolerable drug to continuation-maintenance by pemetrexed alone. Comparing recent randomized phase III studies (PRAMOUNT, AVAPERL and PointBreak), the addition of bevacizumab to a standard regimen of pemetrexed plus platinum induction has enabled more patients to receive maintenance therapy and continuation-maintenance by pemetrexed plus bevacizumab has brought about longer progression-free survival than the maintenance by either of the two drugs. However, further investigation and discussion are required on the viewpoints of overall survival benefit and cost-effectiveness of adding bevacizumab and also we have to explore reliable selection markers for such expensive drugs.