Pemetrexed (Alimta): a promising new agent for the treatment of breast cancer.

Pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, IN) is a new antifolate drug with activity at multiple points in folate metabolism, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. In this way it inhibits the de novo synthesis of both purines and pyrimidines. In phase II studies, pemetrexed has shown good clinical activity as single-agent therapy in patients with advanced breast cancer with or without prior treatment, including patients with prior anthracycline and taxane treatment. Toxicities are primarily neutropenia, mucositis, and skin rash. Hematologic toxicities are markedly reduced by supplementation with vitamin B(12) and folate. Skin rash is ameliorated with prophylactic corticosteroid treatment. Pemetrexed is a promising agent in breast cancer and warrants further investigation in this setting.