Pemetrexed in pancreatic cancer.
New drugs are clearly needed for the treatment of advanced pancreatic cancer, a disease refractory to most chemotherapy. Pemetrexed, a novel antifolate, inhibits thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. Pemetrexed is active against pancreatic cancer cell lines in vitro. Two partial responses in pancreatic cancer patients were observed in a phase I trial of pemetrexed. This led to a phase II trial of pemetrexed in patients with advanced pancreatic cancer. The objective response rate was 6%, 1-year survival rate was 28%, and the toxicities of therapy were mild. Pemetrexed is synergistic with gemcitabine in vitro. In a phase I trial, the pemetrexed/gemcitabine combination was broadly active and well tolerated. A phase II trial of this combination in 42 patients with advanced pancreatic cancer showed promising activity. A 520-patient international randomized phase III trial that compares the pemetrexed/gemcitabine combination with single-agent gemcitabine is currently accruing patients.
Kindler
Hedy Lee
HL
Section of Hematology/Oncology, The University of Chicago, Chicago, IL 60637, USA.
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005492:Folic Acid / Q000008:administration & dosage; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014805:Vitamin B 12 / Q000008:administration & dosage; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D005492:Folic Acid; D013940:Thymidylate Synthase; D014805:Vitamin B 12; D000093542:Gemcitabine