This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a phase I study of pemetrexed (LY231514, Alimta) in children and adolescents with recurrent solid tumors. Pemetrexed is a novel antifolate that inhibits multiple targets. Antimetabolites are cytotoxic drugs structurally similar to naturally occurring molecules necessary for the synthesis of pyrimidines, purines, and nucleic acids. Pemetrexed has anti-tumor activity through inhibition of several key folate-requiring enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT). The study recommendation is to continue to accrue patients and to follow the escalation schema as specified. Once the MTD has been achieved, this agent should be moved forward to the phase II setting
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