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Therapeutic Activity of a Thioether-Lipid Conjugate of 1-ß-D-Arabinofuranosylcytosine in Human Colorectal Cancer Xenografts

Departments of Medicine, Klinikum Rudolf Virchow [R. H.], and Medicine/Hematology and Oncology, Klinikum Steglitz [W. E. B.], Freie Universität, Berlin, Federal Republic of Germany

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 > 2 and T/C < 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 To whom requests for reprints should be addressed, at Division of Oncology, Kantonsspital, Petersgraben 4, CH-4031 Basel, Switzerland.

² Recipient of Grant DFG Be 822/2-6 from Deutsche Forschungsgemeinschaft.

Received 9/16/91. Accepted 1/17/92.