Clinical studies of pemetrexed and gemcitabine combinations.

Pemetrexed (ALIMTA) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent is broadly active in a wide variety of solid tumors, including breast cancer, bladder cancer, mesothelioma, non-small-cell lung cancer, pancreatic cancer and ovarian cancer. Pemetrexed has also shown clinically relevant activity in combination with gemcitabine. This combination has been, and continues to be evaluated for the treatment of a number of malignancies, including non-small cell lung and ovarian cancer. A recently published randomized trial of different sequences has identified the sequence of pemetrexed on day 1 followed by gemcitabine on day 1 and gemcitabine on day 8, every 21 days as the most efficacious and least toxic sequence.