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Antitumor Effect of 1-ß-D-Arabinofuranosylcytosine 5'-Adamantoate (NSC 117614) in L1210 Leukemic Mice¹

The Upjohn Company, Kalamazoo, Michigan 49001

The effects of a new derivative of 1-ß-D-arabinofuranosylcytosine (ara-C), NSC 63878, 1-ß-D-arabinofuranosylcytosine 5'-adamantoate, NSC 117614 (AdO-ara-C), on the survival of L1210 leukemic mice was studied. In all the treatment schedules investigated (single doses, short courses of daily doses, and widely spaced doses), AdO-ara-C was therapeutically more effective than ara-C. For a given total dose, the effectiveness of AdO-ara-C was relatively insensitive to the schedule used. Single dose therapy with AdO-ara-C was almost as effective as therapy with ara-C on an "optimum" schedule (courses of multiple closely spaced doses with appropriate intervals for host recovery). AdO-ara-C was effective when administered i.p. or s.c. The agent is active even when administered as much as 48 hr prior to tumor inoculation. This and other data (e.g., lack of reversal in vivo by deoxycytidine) suggest a sustained action effect. The results are discussed in terms of this hypothesis.

¹ Work supported by Contract PH43-68-1023 with Chemotherapy, National Cancer Institute, NIH, Bethesda, Md. 20014.

Received 7/21/69. Accepted 10/ 9/69.