Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts.
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.[1]References
- Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts. Herrmann, R., Berdel, W.E. Cancer Res. (1992) [Pubmed]
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