Toxicoses associated with administration of mitoxantrone to dogs with malignant tumors

Gregory K. Ogilvie From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Gregory K. Ogilvie in
Current site
Google Scholar
PubMed
Close
 DVM
,
Joyce E. Obradovich From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Joyce E. Obradovich in
Current site
Google Scholar
PubMed
Close
 DVM
,
Robyn E. Elmslie From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Robyn E. Elmslie in
Current site
Google Scholar
PubMed
Close
 DVM
,
David M. Vail From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by David M. Vail in
Current site
Google Scholar
PubMed
Close
 DVM
,
A. S. Moore From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by A. S. Moore in
Current site
Google Scholar
PubMed
Close
 MVSc
,
Charles R. Curtis
Search for other papers by Charles R. Curtis in
Current site
Google Scholar
PubMed
Close
 PhD
,
Rodney C. Straw From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Rodney C. Straw in
Current site
Google Scholar
PubMed
Close
 BVSc
,
Krista Dickinson From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Krista Dickinson in
Current site
Google Scholar
PubMed
Close
,
Mary F. Cooper From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Mary F. Cooper in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Stephen J. Withrow From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (Ogilvie, Obradovich, Elmslie, Vail, Curtis, Straw, Dickinson, Cooper, Withrow), and Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

Search for other papers by Stephen J. Withrow in
Current site
Google Scholar
PubMed
Close
 DVM

Click on author name to view affiliation information

Summary

One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered iv at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P < 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P < 0.001). The performance status (modified Karnofsky performance scheme) of each dog was not adversely affected to a significant extent by mitoxantrone-induced toxicosis until the fifth dose (P = 0.0008). Cardiac toxicosis was not detected. Mitoxantrone was also administered iv to 4 clinically normal dogs, at a dosage of 5 mg/m2 of body surface area, a decrease in the neutrophil count was seen, with the nadir occurring on day 10 (mean ± sem: 1,159 ± 253 cells/μl; range, 480 to 1,680 cells/μl). Tumor-bearing dogs did not seem to have the same degree of myelosuppression (mean ± sem, 6,263 ± 1,230 cells/μl; range, 228 to 18,600 cells/μl).

Summary

One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered iv at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P < 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P < 0.001). The performance status (modified Karnofsky performance scheme) of each dog was not adversely affected to a significant extent by mitoxantrone-induced toxicosis until the fifth dose (P = 0.0008). Cardiac toxicosis was not detected. Mitoxantrone was also administered iv to 4 clinically normal dogs, at a dosage of 5 mg/m2 of body surface area, a decrease in the neutrophil count was seen, with the nadir occurring on day 10 (mean ± sem: 1,159 ± 253 cells/μl; range, 480 to 1,680 cells/μl). Tumor-bearing dogs did not seem to have the same degree of myelosuppression (mean ± sem, 6,263 ± 1,230 cells/μl; range, 228 to 18,600 cells/μl).

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 254 254 106
PDF Downloads 29 29 3
Advertisement