July 1st 2004
The use of chemotherapy in the treatment of early and advancednon–small-cell lung cancer (NSCLC) has increased during the pastdecade. One of the main reasons for the increased acceptance of chemotherapyis the development of several new cytotoxic agents with aunique mechanism(s) of action and high single-agent activity, combinedwith a favorable toxicity profile. Pemetrexed (Alimta) is a novelantifolate that inhibits several enzymes involved in DNA synthesis(thymidylate synthase [TS], dihydrofolate reductase [DHFR], andglycinamide ribonucleotide formyltransferase [GARFT]). Pemetrexed’stoxicity 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 IV over 10 minutes, has shown promising activity, and can safelybe administrated with vitamin supplementation. After registration,single-agent pemetrexed will certainly add to the chemotherapeuticoptions available for pretreated patients and will most likely changesignificantly chemotherapy prescriptions in second-line chemotherapy.In first-line chemotherapy, the role of platinum-based and -free combinationdoublet chemotherapy with pemetrexed still needs to be defined.Phase II data indicate high efficacy combined with favorabletoxicity for pemetrexed in combination with cisplatin, carboplatin(Paraplatin), oxaliplatin (Eloxatin), gemcitabine (Gemzar), andvinorelbine (Navelbine). This review summarizes the clinical experienceobtained thus far during the early clinical development ofpemetrexed in NSCLC.