Pemetrexed: potential role in the adjuvant chemotherapy of non-small cell lung cancer

Platinum-based doublet chemotherapy is now established as a standard of care in the adjuvant treatment of resected stage II and stage IIIA nonsmall cell lung cancer, and seems reasonable also in resected stage IB when the primary tumor measures > or =4 cm. Several issues remain unresolved, however, including individualized selection of both the optimal platinum (cisplatin vs carboplatin), and the optimal nonplatinum drug; and identification of patients who will not need chemotherapy ("surgically cured"), as well as patients who cannot benefit because of inherently drug resistant disease. Furthermore, while efficacy remains a priority, it is also necessary to improve the management of toxicity, both because it may compromise dose intensity and because it carries a risk of morbidity and even mortality. Other issues, such as the role of postoperative radiotherapy, the choice between neoadjuvant and adjuvant approaches, the role of targeted agents, and the possibility of harm and how it can be mediated, also merit serious attention. Finally the durability of benefit, the question of late toxicity, and the importance of smoking cessation are also open questions. I will discuss a potential role for pemetrexed in the adjuvant treatment of early stage nonsmall cell lung cancer with some of these issues in mind.