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 ribonucleotide formyltransferase [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 IV 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.