The pemetrexed/gemcitabine combination in pancreatic cancer.
Gemcitabine has modest antitumor activity in advanced pancreatic cancer. New agents are clearly needed. Pemetrexed (ALIMTA) is a novel antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has shown in vitro activity against pancreatic cancer cell lines. In a Phase I trial of pemetrexed, two patients with pancreatic cancer achieved partial responses on the once every 21 days schedule. A Phase II trial of pemetrexed in patients with advanced pancreatic cancer showed an objective response rate of 6%, a one year survival of 28%, and a mild toxicity profile. The combination of pemetrexed and gemcitabine is synergistic in vitro and was broadly active in a Phase I trial. The pemetrexed/gemcitabine combination was evaluated in a Phase II trial in 42 patients with advanced pancreatic cancer. The promising activity observed in this study has led to an ongoing international, randomized, Phase III trial in 520 patients comparing the pemetrexed/gemcitabine combination with gemcitabine alone.
Kindler
Hedy Lee
HL
Director of Gastrointestinal Oncology, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, USA. hkindler@medicine.bsd.uchicago.edu
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D016019:Survival Analysis; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine