Phase I evaluation of CCNU (lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.     

Permethrin toxicity in cats: a retrospective study of 20 cases

OBJECTIVE: Permethrin is a synthetic pyrethroid widely used in flea control products for small animals. Accidental toxicity can occur with off-label usage, and cats are particularly susceptible. METHODS: Retrospective study of 20 cases of permethrin toxicity in cats treated at an emergency clinic in Brisbane, Queensland from October 2004 to June 2005. RESULTS: The diagnosis of permethrin toxicity was made on the basis of a history of exposure and characteristic clinical signs, including seizures, muscle fasciculations, and tremors. Decontamination and appropriate seizure or muscle fasciculation control were the basis of treatment. The outcome was good after rapid intervention and 19 of the 20 cats were successfully treated, with the only death occurring in a kitten for which treatment was delayed for 24 h. No long-term complications were reported by the cats' owners at 4-month follow-up after discharge from hospital. CONCLUSIONS: Owner education, together with more appropriate product labelling, may help eliminate this problem in the future.     

Treatment-related toxicities in tumor-bearing cats treated with temozolomide alone or in combination with doxorubicin: a pilot assessment

A retrospective study assessing treatment-related toxicities in tumor-bearing cats treated with temozolomide (TMZ) alone or in combination with doxorubicin was conducted. TMZ was administered orally once a day for 5 days every 3 weeks at a dose of 20 mg/cat. Tumor response was evaluated with standard World Health Organization criteria and toxicity was monitored using veterinary co-operative oncology group-common terminology criteria for adverse events (VCOG--CTCAE) criteria. Ten tumor-bearing cats with various types of malignancies were treated with TMZ-based chemotherapy. Eight cats were evaluable for response. Two cats achieved a complete response, one achieved stable disease and five achieved a partial response. Four grade III and one grade IV hematological toxicities, and one grade IV gastrointestinal toxicity were observed. Four cats were euthanased as a result of apparent toxicity. One cat was euthanased as a result of severe and prolonged myelosuppression with fever. Three were euthanased for grade III pleural and pericardial effusions. Effusion was seen in cats treated with higher cumulative dose of TMZ (P = 0.0046). Planned additional case accrual was discontinued because of unacceptable levels of toxicity despite evidence of efficacy in some of the cats. Additional investigation is needed to elucidate this unexpected apparent cumulative toxicity.     

Drug therapy in cats: a therapeutic category approach

The third article of this 4-part series discusses drug therapy in cats by therapeutic category. Specifically, the use of drugs to control infections, pain, fever, inflammation, cancer, and selected parasites is described. In addition, the use of hormonally related drugs and selected miscellaneous drugs in cats is addressed. Drugs emphasized are those for which use in cats is frequently associated with adverse reactions or drugs for which use is limited to illnesses that tend to be unique in cats.     

Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study

BACKGROUND: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial. PURPOSE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors. METHODS: The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached. RESULTS: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days). CONCLUSIONS AND CLINICAL IMPORTANCE: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks.     

Pharmacokinetics and toxicity of zonisamide in cats

With the eventual goal of making zonisamide (ZNS), a relatively new antiepileptic drug, available for the treatment of epilepsy in cats, the pharmacokinetics after a single oral administration at 10mg/kg and the toxicity after 9-week daily administration of 20mg/kg/day of ZNS were studied in healthy cats. Pharmacokinetic parameters obtained with a single administration of ZNS at 10mg/day were as follows: Cmax=13.1microg/ml; Tmax=4.0h; T(1/2)=33.0h; areas under the curves (AUCs)=720.3microg/mlh (values represent the medians). The study with daily administrations revealed that the toxicity of ZNS was comparatively low in cats, suggesting that it may be an available drug for cats. However, half of the cats that were administered 20mg/kg/day daily showed adverse reactions such as anorexia, diarrhoea, vomiting, somnolence and locomotor ataxia.     

Cognitive dysfunction in cats: clinical assessment and management

Increasing numbers of cats are living to become elderly and they commonly develop behavioral changes. The objectives of this article are to consider the possible causes and prevalence of behavioral problems in pet cats, to describe how cognitive dysfunction syndrome (CDS) typically presents, and how its diagnosis and management are often complicated by the concurrent presence of multiple interacting disease processes. The most frequently reported behavioral problems in old cats are loss of litter box training and crying out loudly at night. The most common causes of these problems are CDS, osteoarthritis, systemic hypertension (commonly secondary to chronic kidney disease or hyperthyroidism), hyperthyroidism (even without hypertension), deafness, and brain tumors. These conditions all occur frequently in older cats, many of which suffer from a number of concurrent interacting conditions. Owners and veterinary surgeons often mistake these for "normal aging changes," so many treatable conditions are neglected and go untreated. Almost one third of cats 11 to 14 years of age develop at least one geriatric-onset behavior problem that appears to relate to CDS, and this increases to over 50% for cats 15 years of age or older. For optimum management of elderly cats with behavioral problems, all interacting conditions need to be diagnosed and addressed concurrently with management for CDS.     

Carprofen as an analgesic for postoperative pain in cats: Dose titration and assessment of efficacy in comparison to pethidine hydrochloride

The aim of this study was to titrate the optimal dose of carprofen for single dose usage, for alleviating postoperative pain, under a double-blind and randomised protocol, using both negative and positive controls. Renal tolerance was assessed by screening plasma urea and creatinine. Pre- and postoperative assessment of pain and sedation was made using a dynamic and interactive visual analogue scoring system in 60 cats undergoing ovariohysterectomy. The cats were randomly assigned to one of six groups: (1) carprofen at 1-0 mg/kg subcutaneously (sc); (2) carprofen at 2-0 mg/kg sc; (3) carprofen at 4-0 mg/kg sc; (4) pethidine at 5-0 mg/kg intramuscularly (im), (5) pethidine at 10-0 mg/kg im; and (6) no analgesics (injection of saline). All injections were given postoperatively on tracheal extuba-tion and administered in a double-blind manner. Assessments were made up to 20 hours post extubation. Prior to induction and at 20 hours post extubation, blood samples were taken for laboratory analysis of the urea and creatinine content to check for any adverse effect on renal function. Cats given pethidine did not appear more sedated than the groups receiving carprofen or saline. Cats receiving carprofen were in less pain postoperatively overall, with 4-0 mg/kg being the most effective dose rate (significantly better than the other doses of carprofen at four and eight hours post extubation). The highest dose of pethidine provided significantly better analgesia than the highest dose of carprofen up to two hours post extubation, but from two to 20 hours post extubation carprofen at 4-0 mg/kg provided significantly better analgesia than the pethidine. None of the analgesic regimens appeared to affect renal function adversely, as measured by urea and creatinine levels.     

Comparison of a new device for blood sampling in cats with a vacuum tube collection system - plasma biochemistry, haematology and practical usage assessment

Using paediatric devices to collect venous blood from a cephalic vein in cats offers numerous practical advantages over traditional jugular venepuncture and vacuum closed systems: minimal restraint is required; there is minimal risk of serious injury to the cat; the discomfort associated with venepuncture is reduced by the use of small diameter (25 gauge) needles; very small volumes (200 microl) of blood are extracted; and the risk of vein collapse or haematoma is low. The aim of this study was to compare the haematological and plasma chemistry results obtained from six healthy cats using the two sampling techniques. Five plasma biochemical analytes were measured and a complete haematological examination was performed on each specimen. No clinically relevant difference between the two blood sampling techniques was observed for any variable, indicating that paediatric devices provide a useful alternative to vacuum tubes for venous blood collection in the cat.     

Electrocardiographic assessment of hyperkalemia in dogs and cats

Objective: To determine if electrocardiogram (ECG) changes induced by hyperkalemia in clinical patients correspond with previously reported changes in experimental animals. Design: Prospective clinical study. Setting: Two private practice 24‐hour emergency and critical care facilities. Animals: Fifteen dogs and 22 cats with serum potassium levels >5.5 mEq/L. Interventions: None. Measurements: The following data were collected when hyperkalemia was documented: ECG (n=37), sodium and chloride (mEq/L) (n=35), total magnesium (mg/dL) (n=18), total calcium (mg/dL) (n=30), and venous pH (n=18). Animals were divided into five groups based on severity of hyperkalemia and ECG interpretation included rate, rhythm and P‐QRS‐T evaluation. Main Results: Twenty‐two of 37 (59%) of the ECGs were normal or revealed abnormalities that have not been previously described in conjunction with hyperkalemia. In dogs, there was no correlation (r=0) between potassium blood levels and heart rate (n=15). There was weak correlation (r=0.40; P=0.06) between potassium blood levels and heart rate in cats (n=22). The correlation was stronger (r=0.64; P<0.05) when data were compared in cats with serum potassium level >8.5 mEq/L (Groups 4 and Group 5; n=11). Conclusions: ECGs obtained from ill dogs and cats with hyperkalemia are inconsistent with ECGs from experimentally induced hyperkalemia. It is difficult to determine the clinical relevance of heart rate differences between cats with serum potassium levels >8.5 mEq/L and animals with experimentally induced hyperkalemia; this may be due to the presence of other biochemical abnormalities in diseased animals.     

Tick toxicity in cats caused by Ixodes species in Australia: a review of published literature

Tick toxicity in cats caused by Ixodes holocyclus and related species is a common medical condition on the east coast of Australia. Intoxication typically causes a flaccid ascending neuromuscular paralysis and clinical signs can include anxiety, dysphonia, hind limb weakness and/or ataxia, pupillary dilation, respiratory signs and possible bladder voiding dysfunction. Diagnosis is made with a combination of appropriate clinical signs and visualisation of tick(s) on a thorough body search. Cases are classified clinically using a scoring system, which grades neuromuscular weakness and respiratory compromise. The mainstays of treatment are tick removal, administration of tick antitoxin serum and intensive supportive care. Given a prompt and appropriate management regimen, prognosis is good, according to available literature. Most of the literature concerning tick toxicity in cats is anecdotal in nature and an evidence-based review of what is known of this condition has not previously been published.     

Assessment of melamine and cyanuric acid toxicity in cats.

The major pet food recall associated with acute renal failure in dogs and cats focused initially on melamine as the suspect toxicant. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. The purpose of this study was to characterize the toxicity potential of melamine, cyanuric acid, and a combination of melamine and cyanuric acid in cats. In this pilot study, melamine was added to the diet of 2 cats at 0.5% and 1%, respectively. Cyanuric acid was added to the diet of 1 cat at increasing doses of 0.2%, 0.5%, and 1% over the course of 10 days. Melamine and cyanuric acid were administered together at 0%, 0.2%, 0.5%, and 1% to 1 cat per dose group. No effect on renal function was observed in cats fed with melamine or cyanuric acid alone. Cats dosed with a combination were euthanized at 48 hours after dosing because of acute renal failure. Urine and touch impressions of kidneys from all cats dosed with the combination revealed the presence of fan-shaped, birefringent crystals. Histopathologic findings were limited to the kidneys and included crystals primarily within tubules of the distal nephron, severe renal interstitial edema, and hemorrhage at the corticomedullary junction. The kidneys contained estimated melamine concentrations of 496 to 734 mg/kg wet weight and estimated cyanuric acid concentrations of 487 to 690 mg/kg wet weight. The results demonstrate that the combination of melamine and cyanuric acid is responsible for acute renal failure in cats.     

Ureteral obstructions in dogs and cats: a review of traditional and new interventional diagnostic and therapeutic options

Objective – To describe and review both traditional and newer diagnostic and therapeutic options for canine and feline ureteral obstructions currently being performed clinically in veterinary medicine. Data Sources – A Medline search with no date restrictions was used for this review. Human Data Synthesis – The human literature would support the use of minimally invasive endourological techniques for the treatment of nearly all causes of ureteral obstructions, whenever possible. This typically includes extracorporeal shockwave lithotripsy, intracorporeal lithotripsy via retrograde ureteroscopy or antegrade percutaneous nephroureterolithotomy, ureteral stenting, percutaneous nephrostomy tube placement, and laparoscopic endopyelotomy. Typically open surgery is only suggested in cases of ureteral or gynecological malignancy when en bloc resection is considered a good option, or when various methods of endourological techniques have failed. Veterinary Data Synthesis – The veterinary literature is scarce on the use of interventional endourological techniques for the treatment of ureteral obstructions and has been growing over the last 5 years. The current literature reports the use of extracorporeal shockwave lithotripsy for ureteral stones, as well as the use of ureteral stents for the treatment of trigonal obstructive transitional cell carcinoma, ureterolithiasis, and ureteral strictures. Traditional surgical interventions, like ureterotomy, ureteronephrectomy, and ureteral reimplantation is more vastly reported and accepted. This review will focus on new clinical data using interventional endourological techniques for ureteral obstructions. Conclusions – Various treatment options for ureteral obstructions are now available for veterinary patients, and the trend away from traditional surgical techniques will hopefully be followed now that they are technically and clinically available for dogs and cats.     

Clinical efficacy and safety of a once-daily formulation of carbimazole in cats with hyperthyroidism

O bjective : Evaluation of efficacy and safety of a novel controlled-release formulation of carbimazole in feline hyperthyroidism.
M ethods : A multicentre, self-controlled study in 44 client-owned cats with history and clinical signs of hyperthyroidism, and total thyroxine concentration greater than or equal to 50 nmol/l. Treatment was started at 15 mg once daily, response assessed after 10 days, and 3, 5, 8, 26 and 53 weeks and dose adjusted as required.
R esults : The median dose of carbimazole was 10 mg (range 10 to 15 mg) and 15 mg (5 to 25 mg) once daily after 3 and 53 weeks, respectively. Median total thyroxine concentration dropped significantly from 118 nmol/l (50 to 320 nmol/l) at presentation to 33 nmol/l (n=40) after 10 days, 31 nmol/l (n=34) at 3 weeks and 21 nmol/l (n=18) at 53 weeks. Clinical signs improved or resolved in almost all cats within three weeks after starting treatment. Twenty-one adverse reactions possibly (20) or probably (1) related to treatment were reported. During treatment, increased blood urea nitrogen concentration was observed in 25 per cent of the cats, eosinophilia in 20 per cent and lymphopenia in 16 per cent, while liver enzymes tended to improve.
C linical S ignificance : Once daily administration of controlled-release carbimazole tablets was effective and had expected tolerance in hyperthyroid cats during short- and long-term treatment.     

Epsiprantel, a new tapeworm remedy. Preliminary efficacy studies in dogs and cats

The anthelmintic potential of epsiprantel, 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b-octahydropyrazin [2,1-a] [2]benzapine, was revealed using the tapeworms Dipylidium caninum and Taenia taeniaeformis in the cat, and Taenia pisiformis and T. hydatigena in the dog. Subsequent controlled tests in cats demonstrated oral efficacy of 100% against D. caninum with a single dose of 2.5 mg/kg. Although consistently 100% effective against T. taeniaeformis at 5 mg/kg, a single worm was found in one cat treated at 7.5 mg/kg. In experimental infections of Taenia pisiformis in dogs, 100% activity was achieved from a single oral dose of 1 mg/kg. No adverse reaction or drug-associated toxicity were observed at dose levels used.     

The efficacy of pyrantel pamoate against ascarids and hookworms in cats

The purposes of this study were to evaluate pyrantel pamoate administered orally at 20 mg/kg body weight for the removal of induced or natural infections of Ancylostoma tubaeformae and Toxocara cati in cats and to compare the efficacy of paste (40 mg base/g) and granule (80 mg base/g) formulations. Thirty cats of mixed breeding and various ages with natural and/or induced infections of A. tubaeformae and T. cati were assigned to one of three treatment groups: (1) non-medicated controls; (2) paste formulation at 20 mg base/kg; or (3) granule formulation at 20 mg base/kg. Infections were induced by feeding the cats on carcasses of infected mice. The study was conducted in replicates of at least one animal per treatment per replicate. The study parameters included clinical observations, physical examinations, faecal egg counts and the numbers, species and stages of worms recovered at necropsy. The paste formulation was 99.3% and 99.7% effective in reducing egg counts of Ancylostoma sp. and Toxocara sp. respectively. The granule formulation was 97.7% and 99.9% effective in reducing faecal egg counts of Ancylostoma sp. and Toxocara sp. respectively. When administered in paste form, pyrantel pamoate was 99.5% effective in removing adult Ancylostoma and 100.0% effective against adult Toxocara. The granule formulation was 97.9% effective against Ancylostoma and 100% effective against Toxocara. No toxic effects of either formulation of the drug were noted.