Evaluation of a one-hour saline diuresis protocol for administration of cisplatin to dogs

Gregory K. Ogilvie From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Martin J. Fettman From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Vicki J. Jameson From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Lisa M. Walters From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Mary H. Lafferty From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Mary F. Cooper From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Barbara E. Powers From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Phyllis A. Ciekot From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Stephen W. Atwater From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Stephen J. Withrow From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Jameson, Walters, Cooper, Lafferty, Atwater, Ciekot, Withrow), Pathology (Fettman), and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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SUMMARY

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 ≤ 0.0001) and endogenous (P ≤ 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.

SUMMARY

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 ≤ 0.0001) and endogenous (P ≤ 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.

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