Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin

Background

Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.

Hypothesis/Objectives

We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.

Animals

Fourteen client‐owned dogs were prospectively enrolled.

Methods

Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.

Results

A 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).

Conclusions and Clinical Importance

Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.     

Questionnaire‐based Analysis of Owner‐reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari‐like Malformation and Syringomyelia

Background

Chiari‐like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed.

Objectives

To develop a tool to capture owner‐reported clinical signs for use in clinical trials and to compare owner‐reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI).

Animals

Fifty client‐owned CKCS.

Methods

Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner‐reported findings were compared with neurologic examination findings and presence and severity of SM on MRI.

Results

Thirty‐three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r² = 0.213, P = 0.006) and scratch (r² = 0.104, P = 0.089). Owner‐reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner‐reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001).

Conclusions

The questionnaire and maps may be useful for clinical trials. Lack of association of owner‐reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease.