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  • Author or Editor: Robyn E. Elmslie x
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SUMMARY

Fifteen dogs were given doxorubicin, iv, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (besm) was administered sc to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of besm to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of besm sc: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (g-csf) by enzyme immunoassay. Increasing the dosage and schedule of administration of besm reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given besmdaily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in besm-treated dogs after day 7. Median neutrophil counts of the besm-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12). The median counts decreased below normal (< 3,000 cells/μl) for 1 day in the dogs given besm and doxorubicin, and for 3 days in the dogs that were given only doxorubicin. Four of the 6 dogs not treated with besm and none of those given besm developed serious neutropenia (< 1,500/μl). There was an increase in canine g-csf 4 to 6 hours after besm was administered to dogs at dosages of 0.16 and 0.32 mg/kg. These findings demonstrate that besm is capable of reducing the duration and severity of doxorubicin-induced myelosuppression, and that this may be at least partially mediated by g-csf.

Free access
in American Journal of Veterinary Research

Summary

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, iv) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian.

A partial or complete remission (>50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1).

Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.

Free access
in Journal of the American Veterinary Medical Association

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).

Free access
in Journal of the American Veterinary Medical Association

Summary:

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 at 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body surface, iv. Eleven of these cats were treated concurrently with radiation but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the cat developed progressive disease, or until the cat's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. Although the primary purpose of this study was to determine a clinically useful dosage and to characterize the toxicoses associated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or more treatment modalities prior to inclusion in this study.

The most common 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 attributed to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary edema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment than younger cats (P ≤ 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P ≤ 0.05) more likely to develop signs of toxicosis during the 21-day interval between 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 ≤ 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 non toxic cats. Tumor-bearing cats had some degree of myelosuppression 7 days after they were given mitoxantrone at 6.5 mg/m2, iv (median neutrophil count, 2,440 cells/μl; range, 1,595 to 6,300 cells/μl).

Complete or partial remission (> 50% reduction volume reduction) was obtained in 18.4% (14/76) of cats given 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 carcinoma had a poor response to mitoxantrone, an additional 11 cats with squamous 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 these 11 cats had any signs of toxicosis attributable to mitoxantrone chemotherapy. Eight cats had a complete remission (median, 170 days; range, 28 to 485 days), and 1 had a partial remission that lasted 60 days.

Free access
in Journal of the American Veterinary Medical Association