title: Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts.
abstract: The thioether-lipid conjugate of ara-C, ara-CDP-DL-PTBA, was tested for therapeutic activity in vivo on the growth of seven different xenografts of human colorectal cancers in athymic nu/nu mice. Treatment was started approximately 3 weeks after s.c. transplantation of the tumor when the tumors measured about 0.5 x 0.5 cm. The animals were randomly assigned to treatment with the drug or saline vehicle. The conjugate was given at single doses i.p. of 250 mg/kg/week for 3 weeks. There was no toxicity of the drug at this dose level as observed by clinical aspect, weight loss, or decrease in survival at the end of an experiment. However, ara-CDP-DL-PTBA was highly active in three of seven xenografts, almost completely blocking tumor growth as long as treatment continued with specific growth delay greater than 2 and T/C less than 25%. There was minor growth delay in two further xenografts and no activity at all in the other two xenografts. In conclusion, ara-CDP-DL-PTBA is active in the treatment of human colorectal cancer xenografts at a non-toxic dose level and thus should be considered for clinical testing.
authors.affiliation: Department of Medicine, Klinikum Rudolf Virchow, Freie Universität, Berlin, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010742:Phospholipid Ethers / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D003561:Cytarabine; C063784:ara-CDP-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol