OBJECTIVE Data on the efficacy profiles of pemetrexed monotherapy and pemetrexed plus platinum combination therapy in the non-first-line setting for patients with advanced non-small cell lung cancer (NSCLC) are limited,and previous studies have reported contradictory results.This study investigated and compared the efficacy and toxicity profiles of these two regimens to provide a broader understanding of their dynamics.METHODS Previously treated patients with advanced and/or recurrent NSCLC who received pemetrexed monotherapy or pemetrexed plus platinum combination therapy between January 1,2006,and December 31,2009,at Sun Yat-sen University Cancer Center were evaluated.The primary endpoint of this study was progression-free survival (PFS),whereas the secondary endpoints were overall response rate (ORR),disease control rate (DCR),overall survival (OS),and toxicity.Survival was analyzed using the KaplanMeier method.Univariate analysis was performed to identify the factors potentially influencing OS,and chi-square analysis was carried out to compare ORR and DCR.RESULTS Forty-six patients with advanced and/or recurrent NSCLC were analyzed; of these patients,25 were given pemetrexed monotherapy and 21 received pemetrexed plus platinum combination therapy.The following correspond to the rates recorded for the pemetrexed monotherapy group and the pemetrexed plus platinum group:median PFS,1.97 and 2.3 months (P=0.565); median OS,30.93 and 30.33 months (P=0.877); ORR,8％ (2/25) and 9.5％ (2/21)(P=0.857); and DCR,32％ (8/25) and 57.1％ (12/21) (P=0.09).Univariate analysis revealed that no factor was correlated with OS from NSCLC (P＞0.05 for all).Gastrointestinal toxicity in the pemetrexed plus platinum group was modestly higher than that in the pemetrexed monotherapy group (P=0.034),but other adverse events were similar between the groups.CONCLUSION Compared with pemetrexed monotherapy,pemetrexed plus platinum combination therapy causes more gastrointestinal toxicities and does not exhibit improved efficacy,in terms of ORR,DCR,PFS,and OS,in the non-first-line setting for NSCLC.However,further research with a higher patient population is necessary to validate this finding.