Overview of phase II trials of MTA in solid tumors.

MTA (LY231514, multitargeted antifolate) represents a new class of folate antimetabolites and inhibits multiple enzymes in the purine and thymidine biosynthetic pathways, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. Based on the results of phase I investigation, the dose and schedule of 600 mg/m2 administered intravenously every 21 days was selected to carry into the phase II setting. A number of phase II studies are completed or ongoing in a wide range of tumor types, and encouraging results have been observed in colorectal, breast, non-small cell lung, head and neck, bladder, and cervical cancers.