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.
O'Dwyer
P J
PJ
University of Pennsylvania, Philadelphia 19104, USA.
Nelson
K
K
Thornton
D E
DE
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014565:Urogenital Neoplasms / Q000188:drug therapy
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase