NSCLC accounts for 80% of all cases of
lung cancer, which is the leading cause of
cancer mortality. The majority of NSCLC patients present with advanced, unresectable disease, which remains incurable. In advanced disease,
chemotherapy with
platinum (
cisplatin or
carboplatin) in combination with a third-generation cytotoxic
drug (
vinorelbine,
gemcitabine,
paclitaxel, or
docetaxel) can provide a modest improvement in survival without impairing quality of life. In
chemotherapy-naïve, advanced, non-squamous NSCLC patients, the combination of
bevacizumab with
chemotherapy was shown to produce better outcomes than
chemotherapy alone. Response rates of 20%-40% can now be expected, with a median survival of 8-11 months and a 1-year survival rate of 30%-40%. In second-line treatment,
docetaxel has shown superiority to best supportive care in terms of survival and quality of life. A pooled analysis comparing
docetaxel administered weekly versus 3-weekly found similar survival rates between the schedules and a non-significant reduction in
febrile neutropenia for the weekly regimen.
Pemetrexed, a multitargeted
antifolate agent, has shown clear activity in several
tumors, including
mesothelioma and NSCLC. In a phase III trial, second-line treatment with
pemetrexed demonstrated overall survival comparable to
docetaxel, with a more manageable toxicity profile.