Effects of pulse and continuous intravenous infusion of cis-diamminedichloroplatinum on L1210 leukemia in vivo.
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 (greater than or equal to 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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice
D002945:Cisplatin