Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With Chemotherapy

<jats:sec><jats:title>Purpose</jats:title><jats:p> To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non—small-cell lung cancer (NSCLC) previously treated with chemotherapy. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m<jats:sup>2</jats:sup> intravenously (IV) day 1 with vitamin B<jats:sub>12</jats:sub>, folic acid, and dexamethasone or docetaxel 75 mg/m<jats:sup>2</jats:sup> IV day 1 with dexamethasone every 21 days. The primary end point was overall survival. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P = .105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P < .001), febrile neutropenia (12.7% v 1.9%; P < .001), neutropenia with infections (3.3% v 0.0%; P = .004), hospitalizations for neutropenic fever (13.4% v 1.5%; P < .001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P = .092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P < .001) and all grade alopecia (37.7% v 6.4%; P < .001) compared with patients receiving pemetrexed. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available. </jats:p></jats:sec>