Toxicoses associated with the administration of mitoxantrone to dogs with malignant tumors: A dose escalation study

Gregory K. Ogilvie From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Antony S. Moore From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Changhua Chen From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Phyllis A. Ciekot From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Stephen W. Atwater From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Philip J. Bergman From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Lisa M. Walters From the Comparative Oncology Unit, Departments of Clinical Sciences (Ogilvie, Ciekot, Atwater, Bergman, Walters) and Radiological Health Sciences (Chen), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, and School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536 (Moore).

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Summary

Forty-four dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the chemotherapeutic agent mitoxantrone, when administered at dosages higher than what has been previously reported for use in dogs. After each dose was administered, dogs were evaluated for signs of toxicosis for 3 weeks or until the dog developed progressive disease, died, or was euthanatized. Forty dogs had been refractory to 1 or more treatment modalities (surgery, n = 26; chemotherapy other than mitoxantrone, n = 17; radiation, n = 2) prior to entering this study. Ten dogs were given mitoxantrone at a dosage of 5.5 mg/m2 of body surface, IV, every 3 weeks (39 total doses); 11 were given mitoxantrone at a dosage of 6.0 mg/m2, IV, every 3 weeks (26 total doses); and 23 were given mitoxantrone at a dosage of 6.5 mg/m2, IV, every 3 weeks (70 total doses).

The most common signs of toxicosis were vomiting, anorexia, diarrhea, lethargy, and sepsis secondary to myelosuppression. Two dogs, both of which received the highest dosage, died of complications attributable to mitoxantrone administration. The prevalence of toxicoses was not associated with age, breed, sex, tumor type, number of doses, or dosage. Dogs did develop myelosuppression 7 days after they were given mitoxantrone. Median neutrophil count for dogs that received mitoxantrone at a dosage of 6.5 mg/m2 was 2,800 cells/μl (range, 300 to 4,600 cells/μl); median neutrophil count for dogs that received mitoxantrone at a dosage of 6.0 mg/m2 was 3,800 cells/μl (range, 600 to 10,400 cells/μl); and median neutrophil count for dogs that received mitoxantrone at a dosage of 5.5 mg/m2 was 4,500 cells/μl (range, 1,700 to 16,100 cells/μl).

Summary

Forty-four dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the chemotherapeutic agent mitoxantrone, when administered at dosages higher than what has been previously reported for use in dogs. After each dose was administered, dogs were evaluated for signs of toxicosis for 3 weeks or until the dog developed progressive disease, died, or was euthanatized. Forty dogs had been refractory to 1 or more treatment modalities (surgery, n = 26; chemotherapy other than mitoxantrone, n = 17; radiation, n = 2) prior to entering this study. Ten dogs were given mitoxantrone at a dosage of 5.5 mg/m2 of body surface, IV, every 3 weeks (39 total doses); 11 were given mitoxantrone at a dosage of 6.0 mg/m2, IV, every 3 weeks (26 total doses); and 23 were given mitoxantrone at a dosage of 6.5 mg/m2, IV, every 3 weeks (70 total doses).

The most common signs of toxicosis were vomiting, anorexia, diarrhea, lethargy, and sepsis secondary to myelosuppression. Two dogs, both of which received the highest dosage, died of complications attributable to mitoxantrone administration. The prevalence of toxicoses was not associated with age, breed, sex, tumor type, number of doses, or dosage. Dogs did develop myelosuppression 7 days after they were given mitoxantrone. Median neutrophil count for dogs that received mitoxantrone at a dosage of 6.5 mg/m2 was 2,800 cells/μl (range, 300 to 4,600 cells/μl); median neutrophil count for dogs that received mitoxantrone at a dosage of 6.0 mg/m2 was 3,800 cells/μl (range, 600 to 10,400 cells/μl); and median neutrophil count for dogs that received mitoxantrone at a dosage of 5.5 mg/m2 was 4,500 cells/μl (range, 1,700 to 16,100 cells/μl).

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