Pemetrexed, a multi-target folate antimetabolite, shows clear activity in non-small cell lung cancer. In a phase III study for patients with previously treated advanced non-small cell lung cancer, the efficacy of single-agent pemetrexed, as determined by overall survival, was similar to that of docetaxel. (Hanna et al, 2004) The combination of oxaliplatin and pemetrexed has been of particular interest because it has demonstrated both good efficacy and a tolerable side effect profile. Oxaliplatin is a diaminocyclohexane-containing platinum compound that inhibits DNA replication and transcription by forming DNA adducts. Its mechanism of action is similar to that of the classic platinum drugs, but molecular pharmacology studies suggest that oxaliplatin represents a distinct family of platinum compounds. It has a different cytotoxicity profile from cisplatin and can be safely given in the outpatient setting without hydration therapy. (Raymond et al, 1998) Moreover, oxaliplatin appears to interact synergistically with pemetrexed. (Raymond et al, 2002) Phase I studies evaluated pemetrexed plus oxaliplatin in patients with solid tumors, and showed the regimen was efficacious and well tolerated. (Misset et al, 2004) The combination of oxaliplatin and pemetrexed was compared with carboplatin and pemetrexed as first-line therapy for advanced NSCLC in a randomized phase II study. Response rates were 27 and 33%, respectively, and not statistically different. However, toxicity in the oxaliplatin/pemetrexed arm was quite low, this doublet can be delivered easily and is well tolerated. Furthermore, it results in a 7.3% rate of grade 3/4 neutropenia only and the incidence of febrile neutropenia was 2.4%. Dose reductions occur only in 2.6% cycles. Patients received 95.3% and 100% of the planned weekly mean doses of pemetrexed and oxaliplatin, respectively. (Scagliotti et al, 2005)