Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs

Gregory K. Ogilvie From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences (Ogilvie, Elmslie, Walters), Colorado State University, Fort Collins, CO 80523, Amgen Diagnostics (Ceccheni), Boulder, CO 80301, and Cell Technologies Inc (Pearson), 1668 Valtec Lane, Boulder, CO 80301.

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Robyn E. Elmslie From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences (Ogilvie, Elmslie, Walters), Colorado State University, Fort Collins, CO 80523, Amgen Diagnostics (Ceccheni), Boulder, CO 80301, and Cell Technologies Inc (Pearson), 1668 Valtec Lane, Boulder, CO 80301.

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Marie Cecchini From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences (Ogilvie, Elmslie, Walters), Colorado State University, Fort Collins, CO 80523, Amgen Diagnostics (Ceccheni), Boulder, CO 80301, and Cell Technologies Inc (Pearson), 1668 Valtec Lane, Boulder, CO 80301.

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Lisa M. Walters From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences (Ogilvie, Elmslie, Walters), Colorado State University, Fort Collins, CO 80523, Amgen Diagnostics (Ceccheni), Boulder, CO 80301, and Cell Technologies Inc (Pearson), 1668 Valtec Lane, Boulder, CO 80301.

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Frederick C. Pearson From the Comparative Oncology Unit, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences (Ogilvie, Elmslie, Walters), Colorado State University, Fort Collins, CO 80523, Amgen Diagnostics (Ceccheni), Boulder, CO 80301, and Cell Technologies Inc (Pearson), 1668 Valtec Lane, Boulder, CO 80301.

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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.

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.

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