Evaluation of Dexamethasone as a Chemoprotectant for Chemotherapy-Induced Bone Marrow Suppression in Dogs
ACVIM 2008
Joanne Intile1; K. Rassnick1; D. Bailey1; R. Al-Sarraf2; J. Chretin3; A. Flory1; M. Kiselow1; C. Balkman1; J. Wakshlag1
1Ithaca, NY, USA; 2Fairfield, NJ, USA; 3Los Angeles, CA, USA

In mice and humans, administering corticosteroids prior to chemotherapy can reduce the severity of myelosuppression without reducing antitumor effects.1,2 We hypothesized pretreatment with dexamethasone would reduce the incidence of grade 4 (< 500 cells/µL) neutropenia in dogs treated with CCNU.

Tumor-bearing dogs received dexamethasone (0.1 mg/kg PO q 12h)2,3 for five days, and on the sixth day, CCNU (90 mg/m2). A CBC was performed seven days after CCNU was administered. The historical control included dogs treated with CCNU alone. Comparisons between groups were made using chi-square and Student's t-tests. P <0.05 was considered significant. Dexamethasone pharmacokinetics were quantified by ELISA in four healthy dogs administered a single oral dose of 0.1 mg/kg.

Sixty-seven dogs comprised the historical control. Twenty-five dogs were treated with dexamethasone prior to CCNU. Age, weight, and proportion of dogs with lymphoma (versus other neoplasias) were similar between groups. Ninety percent of historical dogs received chemotherapy prior to CCNU compared to 60% in the dexamethasone-treated group (P = 0.002). Forty-five percent of historical dogs had grade 4 neutropenia while 64% pretreated with dexamethasone had grade 4 neutropenia (P = 0.159). In healthy dogs, peak plasma dexamethasone concentrations were < 80 ng/mL.

Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. In humans, the targeted peak plasma concentration of dexamethasone is 80 ng/mL. Failure to achieve this concentration in dogs could explain results reported here, and we currently are escalating the dosage of dexamethasone.

References

1.  Rinehart J, et al. Cancer Biother Radiopharm 1997;12:101-109;

2.  Rinehart J, et al. Am J Clin Oncol 2003;26:448-458;

3.  Gibbons G, et al. Aust Vet Pract 1988;18:160-164

Speaker Information
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Joanne Intile
Cornell University
Ithaca, NY


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