EXPERIMENTAL CHEMOTHERAPY WITH SUPER-HIGH DOSE CISPLATIN AND SODIUM THIOSULFATE (STS) RESCUE
Its Effect on the Survival and the Nephrotoxicity in Mice
1985 Volume 76 Issue 6 Pages 895-903
Details
1985 Volume 76 Issue 6 Pages 895-903
A systemic chemotherapy with cisplatin (DDP) followed by sodium thiosulfate (STS) was deviced. Basically, STS was given repeatedly 6 hours after DDP administration and metoclopramide, methylprodnisolone and pre-hydration were combined. Effects of this regimen (STS-rescue) on DDP-induced toxicities in BALB/c mice were studied.
The maximal tolerable dose of DDP in mice given DDP alone, DDP with physiologic saline and DDP with STS-rescue was 9.0, 10.5 and 16.5mg/kg, respectively. Likewise, LD50 values were calculated as 12.5, 15 and 20.5mg/kg, respectively. Combination of STS-rescue also increased the resistance of mice to DDP-induced nephrotoxicity measured by BUN. It required approximately 6mg/kg more of DDP to increase its BUN level than in control and hydrated mice.
To my knowledge, this is the first report that demonsrates STS administration even 6 hours after DDP administration can reduce the DDP-induced nephrotoxicity and increase the rate of survival after an otherwise lethal dose of DDP. This success seemed to depend both on combination of metoclopramide and repearted administration of isotonic STS solution.
