Cisplatin is an antineoplastic drug used to treat malignant tumors in human beings
and dogs. Nephrotoxicosis was initially considered dose limiting. The use of saline
loading and hypertonic saline administration protocols allowed dose escalation, reduced
nephrotoxicosis, and increased remission rates in the treatment previously poorly
responsive malignant tumors in human beings.
A pilot study was performed to determine efficacy of 4-hour saline loading in
providing renal protection for dogs receiving high-dose cisplatin (150 mg/m2 IV). Two
beagles were saline loaded (25 ml/kg/hr of 0.9% NaCI, IV) for 4 hours and infused with
cisplatin (150 mg/m2). We demonstrated that high-dose cisplatin (150 mg/m2 IV) can be
administered to dogs without biochemical evidence of acute nephrotoxicosis; however
gastrointestinal toxicoses (fibrinonecrotic enteritis) and severe myelosuppression
(leukopenia) were incompatible with patient survival and therefore, dose limiting.
In another study we compared efficacy of hypertonic saline with normal saline in
preventing nephrotoxicosis associated with administration of high-dose cisplatin (90
mg/m2 IV) to dogs. In this study we demonstrated that a single IV dose of cisplatin (90mg/m2) can be administered to dogs in normal saline (0.9%) or hypertonic saline (7%)
in combination with 4 hour saline loading (25 ml/kg/hr) without evidence of reduced
renal function as measured by exogenous creatinine clearance. Platelet numbers were
significantly increased in dogs that received cisplatin in hypertonic saline.
Nephrotoxicosis was not dose limiting in either study. Future studies should
attempt to determine the efficacy and toxicoses of multiple doses of cisplatin (90 mg/M2
administered in hypertonic saline to tumor bearing dogs.
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