Objective—To characterize oral bioavailability and pharmacokinetic disposition of etoposide when the IV formulation was administered orally to dogs.
Animals—8 tumor-bearing dogs.
Procedures—An open-label, single-dose, 2-way crossover study was conducted. Dogs were randomly assigned to initially receive a single dose of etoposide (50 mg/m2) IV or PO. A second dose was administered via the alternate route 3 to 7 days later. Medications were administered before IV administration of etoposide to prevent hypersensitivity reactions. Oral administration of etoposide was prepared by reconstituting the parenteral formulation with 0.9% NaCl solution and further diluting the reconstituted mixture 1:1 with a sweetening agent. Plasma samples were obtained after both treatments. Etoposide concentrations were measured with a high-performance liquid chromatography assay, and plasma etoposide concentration–time profiles were analyzed by use of noncompartmental methods.
Results—4 dogs had hypersensitivity reactions during IV administration of etoposide. No adverse effects were detected after oral administration. Plasma etoposide concentrations were undetectable in 2 dogs after oral administration. Oral administration of etoposide resulted in significantly lower values for the maximum plasma concentration and the area under the plasma etoposide concentration-versus-time curve, compared with results for IV administration. Oral bioavailability of etoposide was low (median, 13.4%) and highly variable among dogs (range, 5.7% to 57.3%).
Conclusions and Clinical Relevance—Vehicle-related toxicosis can limit the IV administration of etoposide in dogs. The parenteral formulation of etoposide can be safely administered orally to dogs, but routine use was not supported because of low and variable oral bioavailability in this study.
Animals—71 dogs with subcutaneous or intramuscular HSA.
Procedures—Medical records of affected dogs were reviewed. The following factors were evaluated for an association with outcome: dog age and sex, clinical signs, anemia, thrombocytopenia, neutrophilia, tumor stage at diagnosis, achievement of complete excision, intramuscular involvement, presence of gross disease, tumor recurrence, and treatment.
Results—Of the 71 cases identified, 16 (29%) had intramuscular tumor involvement. For all dogs, median time to tumor progression and overall survival time (OST) were 116 and 172 days, respectively; 25% survived to 1 year. Univariate analysis identified presence of clinical signs or metastasis at diagnosis, dog age, tumor size, use of any surgery, and presence of gross disease as predictors of time to tumor progression and OST. There was no significant difference in survival time between dogs with respect to type of HSA. Multivariate analysis confirmed that adequate local tumor control, tumor diameter ≤ 4 cm, presence of metastasis at diagnosis, and presence of gross disease were significantly associated with OST.
Conclusions and Clinical Relevance—Subcutaneous and intramuscular HSA remains a heterogeneous group of tumors that generally carries a poor prognosis. Adequate local control of smaller tumors with no associated clinical signs or metastasis may provide the best chance of long-term survival.
Objective—To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol.
Design—Retrospective case series.
Animals—95 dogs with lymphoma.
Procedures—Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined.
Results—Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days.
Conclusions and Clinical Relevance—Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.
To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone.
109 client-owned dogs recruited from 15 institutions in the United States.
Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined.
Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunopheno-type (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned sub-stage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made. (J Am Vet Med Assoc 2021;259:62–71)