EVALUATION OF A ONE-HOUR SALINE DIURESIS PROTOCOL FOR ADMINISTRATION OF CISPLATIN TO DOGS

A study was undertaken to determine the toxic effects of cisplatin, an antineoplastic agent, when administered immediately after a 1-hour saline diuresis. Four treatments with cisplatin (70 mg/M2 of body surface, q 3 wk) were administered IV to 6 healthy dogs over a 20-minute period after 0.9% NaCl (saline) solution was administered IV for 1 hour at a volume of 132 ml (kg)0.75. Each dog vomited at least once within 8 hours after each treatment was administered. Clinical status, body weight, and food consumption were normal throughout the 12-week study for 5 of the 6 dogs. The sixth dog developed acute renal failure and became acutely blind and deaf within 3 days after the fourth treatment with cisplatin. Serum electrolyte, creatinine, and urea nitrogen values remained within established normal limits in all dogs immediately prior to each treatment, and in 5 of 6 dogs evaluated 3 weeks after the final treatment. The serum creatinine value (3.3 mg/dl) obtained from the Beagle euthanatized 2 weeks after the fourth treatment was above established normal values. Despite normalcy for all but 1 of the creatinine values, serum creatinine concentration obtained 3 weeks after the final treatment with cisplatin was significantly (P = 0.0001) higher than pretreatment values. When compared with data from all other evaluation periods, significant decreases in glomerular filtration rate, as determined by exogenous (P less-than-or-equal-to 0.0001) and endogenous (P less-than-or-equal-to 0.0001) creatinine clearance testing, were identified 3 weeks after the fourth treatment with cisplatin. Neutrophil counts decreased significantly below pretreatment values at the third (P = 0.009), fourth (P < 0.0001), and fifth (P < 0.0001) evaluation period. We concluded that cisplatin can be administered with biochemical evidence, but not necessarily clinical evidence, that renal dysfunction may develop after 4 treatments with cisplatin (70 Mg/M2, IV) are administered to dogs, using a 1-hour diuresis protocol.