Pemetrexed: its promise in treating non-small-cell lung cancer

The use of chemotherapy in the treatment of early and advanced non-small-cell lung cancer (NSCLC) has increased during the past decade. One of the main reasons for the increased acceptance of chemotherapy is the development of several new cytotoxic agents with a unique mechanism(s) of action and high single-agent activity, combined with a favorable toxicity profile. Pemetrexed (Alimta) is a novel antifolate that inhibits several enzymes involved in DNA synthesis (thymidylate synthase [TS], dihydrofolate reductase [DHFR], and glycinamide ribonucleotideformyltransferase [GARFT]). Pemetrexed's toxicity is markedly reduced by folic acid and vitamin B12 supplementation. The compound has been studied extensively in various tumor types, including NSCLC. In NSCLC, pemetrexed at 500 mg/m2, every 3 weeks, given i.v. over 10 minutes, has shown promising activity, and can safely be administrated with vitamin supplementation. After registration, single-agent pemetrexed will certainly add to the chemotherapeutic options available for pretreated patients and will most likely change significantly chemotherapy prescriptions in second-line chemotherapy. In first-line chemotherapy, the role of platinum-based and -free combination doublet chemotherapy with pemetrexed still needs to be defined. Phase II data indicate high efficacy combined with favorable toxicity for pemetrexed in combination with cisplatin, carboplatin (Paraplatin), oxaliplatin (Eloxatin), gemcitabine (Gemzar), and vinorelbine (Navelbine). This review summarizes the clinical experience obtained thus far during the early clinical development of pemetrexed in NSCLC.