Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin

Karina D. Valerius From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Gregory K. Ogilvie From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Martin J. Fettman From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Judy A. Walton From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Kristi Richardson From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Barbara E. Powers From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Elizabeth A. McNiel From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Quinton R. Rogers From the Departments of Clinical Sciences (Valerius, Ogilvie, Walton, Richardson, McNiel) and Pathology (Fettman) and the Diagnostic Laboratory (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and the Department of Physiological Science (Rogers), School of Veterinary Medicine, University of California, Davis 95616.

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Objective

To determine the effectiveness and safety of asparaginase administered SC versus IM for treatment of multicentric lymphoma in dogs receiving doxorubicin.

Design

Prospective study.

Animals

49 dogs with multicentric lymphoma

Procedure

Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, SC or IM. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered SC in 23 dogs and IM in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses

Results

Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between SC and IM groups. For dogs in clinical stage IV, IM administration of asparaginase significantly decreased the number of days to complete remission, compared with SC administration (8 vs 17 days, respectively). For dogs in clinical stage III, IM administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated IM had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated SC. Asparaginase toxicoses were not observed regardless of the route of administration.

Clinical Implications

For dogs with multicentric lymphoma that are receiving doxorubicin, IM treatment with asparaginase is more effective than SC treatment. (J Am Vet Med Assoc 1999;214:353–356)

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