Pemetrexed: a multitargeted antifolate (ALIMTA, LY-231514).
Pemetrexed is a new member of the antifolate class of anticancer drugs. Here we describe how it is activated, its mode of action and its pharmacokinetics. Three single-agent Phase I trials are described with particular reference to the observed spectrum of toxicity but also anticancer activity. Several areas of antitumor activity have been explored further in Phase II trials and these are also reported here, as are early studies of pemetrexed in combination with other anticancer agents. Although the results of Phase III studies are not yet available, pemetrexed has promising activity in a number of solid tumors. We conclude by speculating about its future role in the care of patients.
Cancer Research UK, Department of Medical Oncology, Alexander Stone Building, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. R.Jones@beatson.gla.ac.uk
Robert J
RJ
Jones
Christopher J
CJ
Twelves
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005493:Folic Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D005971:Glutamates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000068437:Pemetrexed; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase