Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development.
BackgroundTransitional 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/ObjectivesWe 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.AnimalsFourteen client‐owned dogs were prospectively enrolled.MethodsTumor 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.ResultsA 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 ImportanceTavocept 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.
Osteochondrodysplasia is a painful, progressive clinical syndrome unique to Scottish fold cats because of a heritable missense mutation in the TRPV4 gene. An 8 yr old male neutered Scottish fold cat was presented for a mass on his hind paw. The mass caused decreased mobility in the metatarsal region and digits and resulted in significant discomfort. Because of extensive skeletal abnormalities attributed to breed-related osteochondrodysplasia, the owner was reluctant to pursue amputation. Radiation therapy was pursued for palliation of pain. After coarsely fractionated external beam radiotherapy resulted in stabilization of the mass with eventual progression after 14 mo, samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid was administered systemically, and the cat showed immediate, whole-body improvement in mobility. Concurrent intestinal and respiratory disease was evaluated and managed. Samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid administration was repeated approximately every 6 mo for three treatments until the cat succumbed to thromboembolic disease attributed to previously diagnosed cardiac disease. Radiation therapy administered using either external beam or bone-seeking radioisotopes can be effective at palliating clinical signs associated with the skeletal abnormalities that accompany this disease.
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