TOXICOSES ASSOCIATED WITH THE ADMINISTRATION OF MITOXANTRONE TO DOGS WITH MALIGNANT-TUMORS - A DOSE-ESCALATION STUDY

Forty-four dogs with histologically confirmed malignant tumors were us ed in a prospective study to determine the toxicity of the chemotherap eutic agent mitoxantrone, when administered at dosages higher than wha t has been previously reported for use in dogs. After each dose was ad ministered, 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 (su rgery, n = 26; chemotherapy other than mitoxantrone, n = 17; radiation , n = 2) prior to entering this study. Ten dogs were given mitoxantron e at a dosage of 5.5 mg/m(2) of body surface, IV, every 3 weeks (39 to tal doses); 11 were given mitoxantrone at a dosage of 6.0 mg/m(2), IV, every 3 weeks (26 total doses); and 23 were given mitoxantrone at a d osage of 6.5 mg/m(2), IV, every 3 weeks (70 total doses). The most com mon signs of toxicosis were vomiting, anorexia, diarrhea, lethargy, an d sepsis secondary to myelosuppression. Two dogs, both of which receiv ed the highest dosage, died of complications attributable to mitoxantr one administration. The prevalence of toxicoses was not associated wit h age, breed, sex, tumor type, number of doses, or dosage. Dogs did de velop myelosuppression 7 days after they were given mitoxantrone. Medi an neutrophil count for dogs that received mitoxantrone at a dosage of 6.5 mg/m(2) was 2,800 cells/mu l (range, 300 to 4,600 cells/mu l); me dian neutrophil count for dogs that received mitoxantrone at a dosage of 6.0 mg/m(2) was 3,800 cells/mu l (range, 600 to 10,400 cells/mu l); and median neutrophil count for dogs that received mitoxantrone at a dosage of 5.5 mg/m(2) was 4,500 cells/mu l (range, 1,700 to 16,100 cel ls/mu l).