TOXICOSES AND EFFICACY ASSOCIATED WITH ADMINISTRATION OF MITOXANTRONETO CATS WITH MALIGNANT-TUMORS

Eighty-seven cats with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of mitoxantrone, a dihydroxyquinone derivative of anthracene, which was administered a t 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body su rface, IV. Eleven of these cats were treated concurrently with radiati on but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the ca t developed progressive disease, or until the cat's quality of life di minished to an unacceptable level as determined by the owner or attend ing veterinarian. Although the primary purpose of this study was to de termine a clinically useful dosage and to characterize the toxicoses a ssociated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or mo re treatment modalities prior to inclusion in this study. The most com mon signs of toxicosis after treatment with mitoxantrone were vomiting , anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures. Two cats died of complications that may have been attrib uted to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary e dema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment th an younger cats (P less-than-or-equal-to 0.05). Cats with signs of tox icosis during the 21-day interval after administration of the first do se of mitoxantrone were significantly (P less-than-or-equal-to 0.05) m ore likely to develop signs of toxicosis during the 21-day interval be tween the second and third doses of mitoxantrone. Similarly, cats that became toxic during the 21-day interval between the second and third doses were significantly (P less-than-or-equal-to 0.05) more likely to become toxic during the 21-day interval between the third and fourth doses. Controlling for age, breed, and dose of mitoxantrone, cats that became toxic after the first treatment were 2.4 times more likely to have poor performance status than the nontoxic cats. Tumor-bearing cat s had some degree of myelosuppression 7 days after they were given mit oxantrone at 6.5 mg/m2, IV (median neutrophil count, 2,440 cells/mul; range, 1,595 to 6,300 cells/mul). Complete or partial remission (> 50% reduction volume reduction) was obtained in 18.4% (14/76) of cats giv en mitoxantrone alone. Remission was recorded in 17.6% (9/51) of cats with carcinoma, 11.8% (2/17) of the cats with lymphoma, and 37.5% (3/8 ) of the cats with sarcoma. Because the cats with squamous cell carcin oma had a poor response to mitoxantrone, an additional 11 cats with sq uamous cell carcinoma were treated concurrently with radiation (44 to 65 Gy, 10 to 15 fractions) over a 3-week period beginning at the time the first dose of mitoxantrone (2.5 to 6 mg/m2) was given. None of the se 11 cats had any signs of toxicosis attributable to mitoxantrone che motherapy. Eight cats had a complete remission (median, 170 days; rang e, 28 to 485 days), and 1 had a partial remission that lasted 60 days.