Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma.

Appendicular osteosarcoma was diagnosed and treated in a pair of littermate Rottweiler dogs, resulting in distinctly different clinical outcomes despite similar therapy within the context of a prospective, randomized clinical trial (NCI-COTC021/022). Histopathology, immunohistochemistry, mRNA sequencing, and targeted DNA hotspot sequencing techniques were applied to both dogs' tumors to define factors that could underpin their differential response to treatment. We describe the comparison of their clinical, histologic and molecular features, as well as those from a companion cohort of Rottweiler dogs, providing new insight into potential prognostic biomarkers for canine osteosarcoma.

Alternating rabacfosadine and doxorubicin for treatment of naïve canine lymphoma.

The current standard of care treatment for canine lymphoma is a multi-agent, CHOP-based chemotherapy protocol. Single agent doxorubicin (DOX) is less burdensome; however, multi-agent chemotherapy protocols are often superior. The recently approved drug rabacfosadine (RAB, Tanovea) provides an attractive option for combination therapy with DOX, as both drugs demonstrate efficacy against lymphoma and possess different mechanisms of action. A previous study evaluating alternating RAB/DOX reported an overall response rate (ORR) of 84%, with a median progression-free survival time (PFS) of 194 days. The aim of this prospective trial was to evaluate the same protocol in an additional population of dogs. Fifty-nine dogs with treatment naïve lymphoma were enrolled. RAB (1.0 mg/kg IV) was alternated with DOX (30 mg/m2 IV) every 21 days for up to six total treatments (3 cycles). Response assessment and adverse event (AE) evaluation were performed every 21 days using VCOG criteria. The ORR was 93% (79% CR, 14% PR). The median time to maximal response was 21.5 days; median PFS was 199 days. T cell immunophenotype and lack of treatment response were predictive of inferior outcomes. AEs were mostly gastrointestinal. Six dogs developed presumed or confirmed pulmonary fibrosis; four were grade 5. One dog experienced grade 3 extravasation injury with RAB that resolved with supportive treatment. These data mirror those of the previously reported RAB/DOX study, and support the finding that alternating RAB/DOX is a reasonable treatment option for canine lymphoma.

ALVAC-fIL2, a feline interleukin-2 immunomodulator, as a treatment for sarcoids in horses: A pilot study.

BACKGROUND: Sarcoid tumors are common in horses and may negatively impact the performance and value of the horse. No known treatment is reliably successful. HYPOTHESES/OBJECTIVES: To determine tolerability, overall response rate, time to response, and progression-free survival of horses with biopsy-confirmed or suspected sarcoids treated with ALVAC-fIL2. ANIMALS: Client-owned horses with measurable, presumed- or biopsy-confirmed sarcoid tumors. METHODS: Prospective pilot study. One milliliter of ALVAC-fIL2 was injected into 4 to 5 areas of the sarcoid(s) in each horse (week 0); this treatment was repeated in weeks 1, 3, and 7. Sarcoids were measured at each visit, and response to treatment was determined according to the Response Evaluation Criteria in Solid Tumors for dogs (v1.0). After the final treatment, horses were reassessed and sarcoids remeasured every 3 months until tumor progression or for a minimum of 1 year if progression was not documented. RESULTS: Fourteen horses were included. Tumor size decreased in 86% of the horses, and the median time to first response was 89 days (range, 34-406 days). Median time to best response was 211 days (range, 56-406 days), but 3 of the sarcoids still were decreasing in size at the time of final evaluation. The median progression-free interval was not reached. Adverse events were minimal and included transient focal inflammation in 2 horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Intratumoral injection of ALVAC-fIL2 has promise as a well-tolerated and effective, tissue-sparing treatment for horses with sarcoid tumors.

A prospective, multi-centre, Veterinary Radiation Therapy Oncology Group study reveals potential efficacy of toceranib phosphate (Palladia) as a primary or adjuvant agent in the treatment of canine nasal carcinoma.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

Retrospective evaluation of intranasal carcinomas in cats treated with external-beam radiotherapy: 42 cases.

BACKGROUND: Little is known regarding the comparative efficacy of various irradiation strategies used to treat intranasal carcinomas (INC) in cats. OBJECTIVES: Investigate outcomes and prognostic factors associated with survival for cats with INC. ANIMALS: Forty-two cats with INC that underwent radiotherapy (RT). METHODS: Single-arm retrospective study. Medical record review for cats with INC that underwent RT at 1 of 7 veterinary RT facilities. Irradiation protocols categorized as: definitive-intent fractionated RT (FRT), definitive-intent stereotactic RT (SRT), and palliative-intent RT (PRT). Median overall survival time (OST) and disease progression-free survival (PFS; documented by advanced transverse imaging, or recurrence of symptoms) were calculated. Associations between tumor stage, RT protocol/intent, and adjunctive treatment usage and outcome were calculated. RESULTS: Cats underwent SRT (N = 18), FRT (N = 8), and PRT (N = 16). In multivariate modeling, cats received definitive-intent treatment (DRT; FRT/SRT) had significantly longer median PFS (504 days, [95% confidence interval (CI): 428-580 days] vs PRT 198 days [95% CI: 62-334 days]; p = 0.006) and median OST [721 days (95% CI: 527-915 days) vs 284 days (95% CI: 0-570 days); p = 0.001]). Cats that underwent second DRT course at time of recurrence lived significantly longer than cats that received 1 RT course (either DRT or PRT [median OST 824 days (95% CI: 237-1410 days) vs 434 days (95% CI: 277-591 days); p = .028]). CONCLUSION: In cats with INC, DRT is associated with prolonged OST and PFS as compared to PRT. If tumor progression occurs, a second course of DRT should be considered.

Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials.

While current lymphoma therapies induce remission in most dogs, drug-resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9-(2-phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty-three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T-cell immunophenotype and corticosteroid pre-treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG-CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.

Indirect computed tomography lymphangiography with aqueous contrast for evaluation of sentinel lymph nodes in dogs with tumors of the head.

Sentinel lymph node evaluation is widely used in human medicine to evaluate the first lymph node(s) to which a tumor drains. Sentinel lymph node biopsy allows avoidance of extensive lymphadenectomies in cases where the sentinel lymph node is negative for metastasis, thereby reducing patient morbidity. It has been shown that regional lymph nodes are not always the sentinel lymph node, thus identification and sampling of sentinel lymph nodes allows for more accurate staging, which is critical for treatment and prognostication in dogs with cancer. The objective of this prospective, pilot study was to determine if indirect computed tomography (CT) lymphangiography with aqueous contrast agent would successfully allow identification of sentinel lymph nodes in dogs with masses on the head. Eighteen dogs underwent CT lymphangiography. The sentinel lymph node was successfully identified within 3 min of contrast injection in 16 dogs (89%). Compression of lymphatic vessels from endotracheal tube ties and/or the patient's own body weight delayed or prevented identification of sentinel lymph nodes in two dogs (11%). Computed tomography lymphangiography with aqueous contrast can be used successfully to rapidly identify sentinel lymph nodes in dogs with masses on the head.

Eosinophilic leukemia in three African pygmy hedgehogs ( Atelerix albiventris) and validation of Luna stain.

Neoplasia is usually encountered in the African pygmy hedgehog at a mean age of 3.5 y, and malignancy is common. Myelogenous leukemias are rarely reported in hedgehogs. We describe 3 cases of eosinophilic leukemia in adult, middle-aged (mean age: 2.3 y) hedgehogs, for which prognosis appears grave. In 1 case, attempted treatment was unsuccessful, and in all 3 cases, the disease course was rapid and all died soon after diagnosis. Blood smear evaluation, along with complete blood count, was critical in making the diagnosis in all cases. Luna stain was validated and used to better visualize eosinophils in cytologic and histologic sections. Electron microscopy confirmed the presence of specific granules in hedgehog eosinophils.

Vaccine-associated feline sarcoma: current perspectives.

Feline injection site sarcomas (FISS; also known as vaccine-associated sarcomas) have been recognized for >20 years. Although uncommon, these tumors are iatrogenic, and vaccination against rabies and feline leukemia virus is perhaps the most common inciting cause. The exact etiopathogenesis is unknown, but it is widely accepted that inflammation induced by vaccines or other injections likely plays a critical role in tumor development. Injection site sarcomas are extremely locally invasive. Multimodal therapy, incorporating combinations of surgery, radiation therapy, and sometimes chemotherapy or immunotherapy, is recommended. However, tumor recurrences are common even with aggressive treatment, and many cats with FISS ultimately succumb to this devastating disease. While vaccination protocols play an important role in the management and control of infectious disease, veterinarians must be diligent in following established vaccination guidelines to minimize individual patient risk of FISS development. Early tumor detection and client education are also vital in the successful treatment of FISS.

A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.

Outcomes of dogs undergoing limb amputation, owner satisfaction with limb amputation procedures, and owner perceptions regarding postsurgical adaptation: 64 cases (2005-2012).

OBJECTIVE: To evaluate outcomes of dogs and owner satisfaction and perception of their dogs' adaptation following amputation of a thoracic or pelvic limb. DESIGN: Retrospective case series. ANIMALS: 64 client-owned dogs. Procedures-Medical records of dogs that underwent limb amputation at a veterinary teaching hospital between 2005 and 2012 were reviewed. Signalment, body weight, and body condition scores at the time of amputation, dates of amputation and discharge from the hospital, whether a thoracic or pelvic limb was amputated, and reason for amputation were recorded. Histologic diagnosis and date of death were recorded if applicable. Owners were interviewed by telephone about their experience and interpretation of the dog's adaptation after surgery. Associations between perioperative variables and postoperative quality of life scores were investigated. RESULTS: 58 of 64 (91%) owners perceived no change in their dog's attitude after amputation; 56 (88%) reported complete or nearly complete return to preamputation quality of life, 50 (78%) indicated the dog's recovery and adaptation were better than expected, and 47 (73%) reported no change in the dog's recreational activities. Body condition scores and body weight at the time of amputation were negatively correlated with quality of life scores after surgery. Taking all factors into account, most (55/64 [86%]) respondents reported they would make the same decision regarding amputation again, and 4 (6%) indicated they would not; 5 (8%) were unsure. CONCLUSIONS AND CLINICAL RELEVANCE: This information may aid veterinarians in educating clients about adaptation potential of dogs following limb amputation and the need for postoperative weight control in such patients.

Relationship between Small Animal Intern Rank and Performance at a University Teaching Hospital.

The purpose of this study was to determine if there is a relationship between selection committee rankings of internship applicants and the performance of small animal interns. The hypothesis was that there would be a relationship between selection committee rank order and intern performance; the more highly an application was ranked, the better the intern's performance scores would be. In 2007, the Department of Small Animal Medicine and Surgery instituted a standardized approach to its intern selection process both to streamline the process and to track its effectiveness. At the end of intern years 2010-2014, every faculty member in the department was provided an intern assessment form for that year's class. There was no relationship between an individual intern's final rank by the selection committee and his/her performance either as a percentile score or a Likert-type score (p=.25, R2=0.04; p=0.31, R2=0.03, respectively). Likewise, when interns were divided into the top and bottom quartile based on their final rank by the selection committee, there was no relationship between their rank and their performance as a percentile score (median rank 15 vs. 20; p=.14) or Likert-type score (median rank 14 vs. 19; p=.27). Institutions that use a similar intern selection method may need to reconsider the time and effort being expended for an outcome that does not predict performance. Alternatively, specific criteria more predictive of performance outcomes should be identified and employed in the internship selection process.

An integrated widefield imaging and spectroscopy system for contrast-enhanced, image-guided resection of tumors.

UNLABELLED: Tumor recurrence following surgery is a common and unresolved medical problem of great importance since surgery is the most widely used treatment for solid-mass tumors worldwide. A contributing factor to tumor recurrence is the presence of residual tumor remaining at or near the surgical site following surgery. GOAL: The primary objective of this study was to develop and evaluate an image-guided surgery system based on a near-infrared, handheld excitation source and spectrograph in combination with a widefield video imaging system. METHODS: This system was designed to detect the fluorescence of near-infrared contrast agents and, in particular, indocyanine green (ICG). The imaging system was evaluated for its optical performance and ability to detect the presence of ICG in tumors in an ectopic murine tumor model as well as in spontaneous tumors arising in canines. RESULTS: In both settings, an intravenous ICG infusion provided tumor contrast. In both the murine models and surgical specimens from canines, ICG preferentially accumulated in tumor tissue compared to surrounding normal tissue. The resulting contrast was sufficient to distinguish neoplasia from normal tissue; in the canine surgical specimens, the contrast was sufficient to permit identification of neoplasia on the marginal surface of the specimen. CONCLUSION: These results demonstrate a unique concept in image-guided surgery by combining local excitation and spectroscopy with widefield imaging. SIGNIFICANCE: The ability to readily detect ICG in canines with spontaneous tumors in a clinical setting exemplifies the potential for further clinical translation; the promising results of detecting neoplasia on the marginal specimen surface underscore the clinical utility.

In vitro efficacy of doxorubicin and etoposide against a feline injection site sarcoma cell line.

Feline injection site sarcoma (ISS) is a locally invasive tumor, in which surgical treatment is frequently combined with radiation or chemotherapy to improve tumor control. The focus of this study was to evaluate the cytotoxic effects of doxorubicin or etoposide on a feline injection site sarcoma cell line (JB) and to assess the impact of combining these drugs on cell death and cell cycle. Both single agent and combination drug administration increased cell death and significantly reduced the number of viable cells. Cells in G0/G1 were significantly reduced while the G2/M fraction was significantly increased following treatment. Collectively, combining doxorubicin and etoposide at the lower EC yielded comparable results to the EC50 of either drug alone in degree of cytotoxicity, level of apoptosis, and % of cells in G2/M. The results of this study indicate that doxorubicin and etoposide alone and in combination differentially alter ISS cell viability and cycle.

Ulnar osteosarcoma in dogs: 30 cases (1992-2008).

OBJECTIVE: To examine the biological behavior of ulnar osteosarcoma and evaluate predictors of survival time in dogs. DESIGN: Retrospective case series. ANIMALS: 30 dogs with primary ulnar osteosarcoma. PROCEDURES: Medical records were reviewed. Variables recorded and examined to identify predictors of survival time were signalment, tumor location in the ulna, tumor length, serum alkaline phosphatase activity, surgery type, completeness of excision, tumor stage, tumor grade, histologic subtype, development of metastases, and use of chemotherapy. RESULTS: 30 cases were identified from 9 institutions. Eleven dogs were treated with partial ulnar ostectomy and 14 with amputation; in 5 dogs, a resection was not performed. Twenty-two dogs received chemotherapy. Median disease-free interval and survival time were 437 and 463 days, respectively. Negative prognostic factors for survival time determined via univariate analyses were histologic subtype and development of lung metastases. Telangiectatic or telangiectatic-mixed subtype (n = 5) was the only negative prognostic factor identified via multivariate analysis (median survival time, 208 days). Dogs with telangiectatic subtype were 6.99 times as likely to die of the disease. CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis for ulnar osteosarcoma in this population was no worse and may have been better than the prognosis for dogs with osteosarcoma involving other appendicular sites. Partial ulnar ostectomy was associated with a low complication rate and good to excellent function and did not compromise survival time. Telangiectatic or telangiectatic-mixed histologic subtype was a negative prognostic factor for survival time. The efficacy of chemotherapy requires further evaluation.

Dexrazoxane treatment of doxorubicin extravasation injury in four dogs.

CASE DESCRIPTION: 4 dogs were treated with dexrazoxane for known or suspected doxorubicin extravasation. Records were retrospectively reviewed. Doses and number of doses of dexrazoxane were variable. Dexrazoxane was administered within 2 hours after known extravasation in 3 dogs and 48 hours after suspected extravasation in 1 dog. Additional medical treatments included tissue cooling in all dogs, topically administered dimethyl sulfoxide ointment in 3, and orally administered piroxicam in 1. CLINICAL FINDINGS: Mild erythema and edema at the extravasation site developed within 1 to 6 days after extravasation in the 3 dogs that received dexrazoxane within 2 hours after extravasation. Extensive tissue necrosis occurred in the dog treated 48 hours after suspected extravasation. TREATMENT AND OUTCOME: Only the dog with severe tissue necrosis required surgical intervention. Lesions in the other 3 dogs resolved with medical management alone. All dogs survived the event. CLINICAL RELEVANCE: To date, use of dexrazoxane in the management of doxorubicin extravasation has not been reported in dogs. Treatment was successful in 3 of 4 patients. The most effective dosage and timing of administration are unknown; however, there is evidence to suggest that administration within 6 hours after the event is warranted. Further studies are needed to confirm efficacy and to optimize use of this drug in the prevention and treatment of anthracycline extravasation injury in veterinary patients.

Assessment of plasma uracil-to-dihydrouracil concentration ratio as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency.

OBJECTIVE: To determine and compare the ratio of uracil (U) to dihydrouracil (UH(2)) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency. ANIMALS: 101 client- and shelter-owned dogs. PROCEDURES: Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency. For each dog, a blood sample was collected into an EDTA-containing tube; plasma U and UH(2) concentrations were determined via UV high-performance liquid chromatography, and the U:UH(2) concentration ratio was calculated. Data were compared among dogs grouped on the basis of sex, clinical group assignment, reproductive status (sexually intact, spayed, or castrated), and age. RESULTS: Mean ± SEM U:UH(2) concentration ratio for all dogs was 1.55 ± 0.08 (median, 1.38; range, 0.4 to 7.14). In 14 (13.9%) dogs, the U:UH(2) concentration ratio was considered abnormal (ie, > 2). Overall, mean ratio for sexually intact dogs was significantly higher than that for neutered dogs; a similar difference was apparent among males but not females. Dogs with ratios > 2 and dogs with ratios ≤ 2 did not differ significantly with regard to sex, clinical group, reproductive status, or age. CONCLUSIONS AND CLINICAL RELEVANCE: Determination of the U:UH(2) concentration ratio was easy to perform. Ratios were variable among dogs, possibly suggesting differences in dihydropyrimidine dehydrogenase activity. However, studies correlating U:UH(2) concentration ratio and fluoropyrimidine antimetabolite drug tolerability are required to further evaluate the test's validity and its appropriate use in dogs.