Gemcitabine and pemetrexed disodium combinations in vitro and in vivo.
Pemetrexed disodium (ALIMTA) is a novel antimetabolite that inhibits at least three folate-dependent enzymes, thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed disodium is broadly active in a wide variety of solid tumours, including non-small cell lung, breast, bladder, head and neck and ovarian cancers. Gemcitabine is a broadly active pyrimidine nucleoside antimetabolite, which is approved for the treatment of pancreatic and non-small cell lung cancers. Three preclinical studies have been reported that show cytotoxic synergy between gemcitabine and pemetrexed. Clinical activity with this combination has been observed in a phase I study, with partial responses in three of five patients previously treated for non-small cell lung cancer. An international phase II study of this combination in non-small cell lung cancer is ongoing.
Adjei
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Division of Medical Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. adjei.alex@mayo.edu
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine