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Effects of Pulse and Continuous Intravenous Infusion of cis-Diamminedichloroplatinum on L1210 Leukemia in Vivo¹

Division of Neoplastic Diseases, Departments of Medicine [R. E. M., M. J. S.] and Biochemistry [R. E. M.], New York Medical College, Valhalla, New York 10595

The in vivo effects of cis-diamminedichloroplatinum on L1210 leukemia were determined using DNA content distribution analysis by flow microfluorometry and pulse [³H]thymidine labeling indices. Pulse and continuous infusion schedules were investigated. Pulse cis-diamminedichloroplatinum (2 and 6 mg/kg) resulted in progression delay of cells in S and G₂ phases and at higher doses ( 12 mg/kg) in G₁ as well. Equivalent total doses administered by continuous infusion over 24 to 72 hr delayed cells in G₂ with little apparent affect on G₁ or S progression. A maximum survival of 70% increased life span over controls was achieved with a 12-mg/kg pulse. Infusion doses at least 2-fold higher were required to achieve similar increases in survival. Cell cycle changes did not predict for therapeutic benefit, suggesting that, at suboptimal doses, cells were capable of repair. The therapeutic index for both modes of administration was narrow.

¹ Supported by Grant CA-27719 from the National Cancer Institute, NIH, Department of Health, Education, and Welfare; the "Dr. I." Fund Foundation, New York, N. Y.; and The Cancer Chemotherapy Foundation, New York, N. Y.

² To whom requests for reprints should be addressed.

Received 10/10/80. Accepted 9/14/81.