A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane

Background: Trilostane is a recognized treatment for canine pituitary‐dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal‐dependent hyperadrenocorticism (ADH) is unknown. Objectives: To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. Animals: Thirty‐seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). Methods: Retrospective analysis of clinical records. Results: There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95–528 days), whereas it was 102 days (95% CI 43–277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). Conclusions and Clinical Importance: The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.     

A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism

The survival times of 148 dogs treated for pituitary-dependent hyperadrenocorticism were studied using clinical records from 3 UK veterinary centers between 1998 and 2003. Of these animals, 123 (83.1%) were treated with trilostane, while 25 (16.9%) were treated with mitotane. Treatment groups were compared using t-tests and analysis of variance (or their nonparametric equivalents) and chi-square tests. Survival data were analyzed using Kaplan-Meier survival plots and Cox proportional hazard methods. There was no significant difference between the population attributes from each center or between treatment groups. The median survival time for animals treated with trilostane was 662 days (range 8-1,971) and for mitotane it was 708 days (range 33-1,399). There were no significant differences between the survival times for animals treated with trilostane and those treated with mitotane. In the multivariable model (including drug, center, breed group, weight, diagnostic group, and age at diagnosis), only age at diagnosis and weight were significantly negatively associated with survival. Importantly, there was no significant effect of drug choice on survival.     

Results of non-selective adrenocorticolysis by o,p'-DDD in 129 dogs with pituitary-dependent hyperadrenocorticism

One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of o,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first followup examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side-effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent CI: 71 to 87 per cent), the two-year survival was 69 per cent (95 per cent CI: 59 to 78 per cent), and the three-year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dog, and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time.     

Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism

The efficacy of trilostane in the treatment of canine pituitary-dependent hyperadrenocorticism (PDH) was evaluated in 78 dogs with the condition which were treated for up to three years. The drug appeared to be well tolerated by almost all the dogs, and only two developed clinical signs and biochemical evidence of hypoadrenocorticism. Polyuria and polydipsia completely resolved in 70 per cent of the dogs that had these problems, and skin changes resolved in 62 per cent of the dogs that had skin abnormalities. There was a significant reduction (P<0.001 in each case) in both the mean basal and post-adrenocorticotrophic hormone (ACTH) cortisol concentrations after a mean of 12.3 days of treatment. The post-ACTH cortisol concentration decreased to less than 250 nmol/litre in 81 per cent of the dogs within one month of the start of treatment and in another 15 per cent at some later time. The median survival time of the 26 dogs which died was 549 days, and 51 of the dogs were alive at the completion of the study. One was lost to follow up after 241 days treatment.     

Long‐Term Survival of Dogs with Adrenal‐Dependent Hyperadrenocorticism: A Comparison between Mitotane and Twice Daily Trilostane Treatment

Background

Treatment of adrenal‐dependent hyperadrenocorticism (ADH) involves either surgical resection of the adrenal tumor or medical therapy. For many years, mitotane has been considered the medical treatment of choice for dogs with ADH.

Objectives

The aim of this study was to determine survival and prognostic factors for dogs with ADH treated with mitotane and trilostane.

Animals

Twenty‐six dogs with ADH were included in the study.

Methods

Fourteen dogs were treated with mitotane and 12 dogs were treated with trilostane. Medical records were reviewed. Epidemiologic factors, signalment, clinicopathologic abnormalities, endocrine test results, and treatment protocols were evaluated to identify potential predictive factors of overall survival time.

Results

Survival times of dogs treated with mitotane (median, 15.6 months) or trilostane (median, 14.0 months) were not significantly different. Using univariate analysis, age and postadrenocorticotropic hormone cortisol concentrations were inversely correlated with survival time. The multivariate model also identified weakness at presentation as a negative prognostic indicator.

Conclusion and Clinical Importance

The type of medical treatment (mitotane versus trilostane) does not influence survival time in dogs with ADH; therefore, trilostane, a drug with less frequent and milder adverse effects, might be used as the primary medical treatment when adrenalectomy cannot be performed.     

Long-term efficacy of trilostane administered twice daily in dogs with pituitary-dependent hyperadrenocorticism

Trilostane is considered an efficacious and safe medication for canine pituitary-dependent hyperadrenocorticism (PDH). Its recommended frequency of administration is once daily. In this prospective study, the efficacy, toxicity, and long-term outcome of trilostane administered twice daily per os were evaluated in 44 dogs with PDH. Mean initial dose was 3.1 mg/kg q 12 hours, and mean final dose was 3.2 mg/kg q 12 hours. The final total daily dose was lower than previously reported for once-daily administration. The mean survival time for affected dogs was 930 days.     

The use of trilostane for the treatment of alopecia X in Alaskan malamutes

Three Alaskan malamutes with hair loss and slightly elevated blood concentrations of 17-hydroxyprogesterone after stimulation with adrenocorticotropic hormone (ACTH) were treated with trilostane. Trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, was given twice daily at a dose of 3.0 to 3.6 mg/kg per day orally for 4 to 6 months. Routine ACTH stimulation tests were performed over 8 months to evaluate the degree of adrenal function suppression. Treatment with trilostane led to complete hair regrowth in all three dogs within 6 months. No adverse effects associated with trilostane were recognized.     

Efficacy, safety and palatability of a new broad-spectrum anthelmintic formulation in dogs

The efficacy, safety and palatability of a new flavoured chewable anthelmintic tablet were investigated in dogs. The efficacy, based on worm counts, of a single recommended therapeutic dose (RTD) of 5 mg pyrantel + 20 mg oxantel + 5 mg praziquantel/kg bodyweight was assessed in experimental infections (EI) and natural infections (NI) with Trichuris vulpis, Echinococcus granulosus and Toxocara canis. For T vulpis, the efficacy of the treatment was 99.3 per cent in EI (comparing groups of six treated and six control dogs) and 100 per cent in NI (nine treated and nine control dogs). For E granulosus, the efficacy was more than 99.9 per cent in EI (11 treated and 11 control dogs). For T canis, the efficacy was 94.3 per cent in EI (10 treated and 10 control dogs) and 100 per cent in NI (12 treated and 13 control dogs). In a field study, Ancylostoma caninum (11 dogs) and T canis (11 dogs) faecal egg counts were reduced by more than 99 per cent, and in eight dogs with Dipylidium caninum proglotides in the faeces the efficacy was 100 per cent. The tablets were readily consumed by 56 of 64 (87.5 per cent) privately owned dogs. Safety was assessed in groups of six dogs treated either once with twice the RTD, once with six times the RTD, with twice the RTD on three consecutive days, or untreated. There were no significant differences in blood parameters between the groups, and no abnormal clinical findings. Two dogs treated with six times the RTD vomited, but no vomiting was observed when administration was repeated two days later.     

Efficacy of licofelone in dogs with clinical osteoarthritis

To evaluate the effect of licofelone, an arachidonic acid substrate with combined inhibitory activity against 5-lipoxygenase and cyclooxygenases 1 and 2, a double-blind, randomised and placebo-controlled study was conducted in 33 client-owned dogs that were lame owing to hindlimb osteoarthritis. Seventeen of the dogs received a placebo and 16 were treated with 2.5 mg/kg licofelone twice a day for 28 days. The dogs' lameness was assessed on a visual analogue scale (vas), and by force plate analyses at baseline and 14 and 28 days after starting the treatment. After 14 days the mean (se) change in peak vertical force in the licofelone-treated dogs (1.7 [0.8] per cent bodyweight) was significantly greater (P<0.05) than in the placebo-treated dogs (-0.3 [0.6] per cent bodyweight), and after 28 days the difference had increased. In contrast, the dogs' lameness, as assessed by the vas values, had decreased significantly over baseline in both the treated and control groups.     

Long-term efficacy and safety of firocoxib in the treatment of dogs with osteoarthritis

Thirty-nine client-owned dogs with osteoarthritis were treated with 5 mg/kg firocoxib administered orally, once a day for 52 weeks. Veterinary examinations were performed on approximately days 0, 15, 90, 180, 270 and 360. Twenty-five dogs completed the study. The withdrawal rate associated with gastrointestinal side effects was low (5.1 per cent of dogs). Based on the owners' assessment, 82 per cent of the dogs had improved at day 15, 84 per cent of the 32 remaining dogs had improved at day 90, and 96 per cent of the 25 dogs that completed the trial had improved at day 360. During this trial, 12 (48 per cent) of the 25 remaining dogs showed an improvement in their lameness from day 90 to day 360 (P<0.05).     

Canine intranasal tumours treated with alternating carboplatin and doxorubin in conjunction with oral piroxicam: 29 cases

Few veterinary studies have evaluated the response to chemotherapy treatment of canine intranasal tumours, while many have focused on the efficacy of radiation therapy. Given the higher costs and limited access to radiation therapy, alternative treatment options are needed. The study describes a cohort of dogs with histologically confirmed intranasal tumours treated with chemotherapy as a sole therapy. This retrospective study was conducted using data from the Melbourne Veterinary Specialist Centre (MVSC) database between 2004 and 2017. Dogs with a histologically confirmed intranasal tumour who received chemotherapy treatment were included. Signalment, presenting signs, tumour type, chemotherapy details, adverse events (AEs) and survival times were reviewed. Twenty‐nine dogs met the inclusion criteria. Overall median survival time for dogs in the study was 234 days (range 12‐1698 days). Median survival for dogs with adenocarcinoma or carcinoma (n = 12) was 280 days, transitional cell carcinoma (n = 6) 163 days, squamous cell carcinoma, anaplastic carcinoma or undifferentiated carcinoma (n = 7) 59 days and all sarcomas (n = 4) 448 days. Adverse events were reported following 28% of treatments and 69% of dogs experienced at least one AE. Twenty four per cent of all dogs experienced grade 3 or 4 toxicities. The chemotherapy protocol was generally well tolerated. The study suggests potential benefit in the use of chemotherapy for dogs with adenocarcinoma, carcinoma and sarcoma.     

Thirteen-week dose-intensifying simultaneous combination chemotherapy protocol for malignant lymphoma in dogs

This prospective study aimed to record the toxicity profile of a dose-intensifying simultaneous chemotherapy (DISC) protocol for lymphoma in dogs. Remission rates and the duration of the protocol were also evaluated. Twenty-one dogs were studied. Diagnosis was based on cytological or histological assessments. The DISC protocol is a 13-week maintenance-free protocol. L-Asparaginase (400 iu/kg) was administered subcutaneously on day 1, followed by weekly simultaneous intravenous administration of vincristine (0.7 mg/m(2) = 100 per cent), cyclophosphamide (200 mg/m(2) = 100 per cent) and doxorubicin (30 mg/m(2) = 100 per cent) at a starting dose level of 33 per cent. Dose levels were given twice and then increased by 5 to 7 per cent if grade 0 or I toxicities were seen, to a maximum dose level of 60 per cent. Two dogs experienced a grade IV toxicity (asymptomatic neutropenia in one dog and sepsis in the other). Two episodes of asymptomatic grade III thrombocytopenia and one episode of neutropenia were recorded. Other toxic events were infrequent and mild. Only one dog required hospitalisation for less than 72 hours. Seventeen dogs (80.9 per cent) achieved complete remission, one (4.8 per cent) achieved partial remission, two (9.5 per cent) had stable disease and in one (4.8 per cent) disease progressed.     

Clinical evaluation of firocoxib and carprofen for the treatment of dogs with osteoarthritis

A double-blind, randomised, controlled, multicentre field study was conducted to compare the safety and efficacy of firocoxib chewable tablets and carprofen tablets in 218 dogs with osteoarthritis. Firocoxib is a non-steroidal anti-inflammatory drug with more than 350-fold selectivity in dogs for the inducible isoform of the enzyme cyclo-oxygenase-2. The efficacy, tolerance and ease of administration of firocoxib (5 mg/kg/day) and carprofen (4 mg/kg/day) were assessed by the owners and the attending veterinarians during 30 days of treatment. The efficacy was assessed in terms of the dogs' overall scores at the end of the treatment, based on the veterinarians' assessment of lameness, pain on manipulation/palpation, range of motion, and joint swelling; 92.5 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved. The reduction in lameness in the dogs treated with firocoxib was significantly greater than in the dogs treated with carprofen. The owners' evaluations were that 96.2 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved, and this difference was statistically significant.     

Therapy of difficult cases of canine pyoderma with marbofloxacin: a report of 39 dogs

Thirty-nine dogs with severe and/or recurrent lesions of pyoderma were treated with marbofloxacin at an average dosage of 2.12 mg/kg bodyweight, once daily, for time periods varing from 10 to 213 days. Forty-seven strains of bacteria, isolated from 34 cultures, were tested for sensitivity to various antibiotics. At day 0, no resistance to marbofloxacin was found, but one refractory case, a strain of Staphylococcus intermedius resistant to marbofloxacin, was cultured at day 28. Thirty-three dogs (84.6 per cent) showed an excellent response (cure), one (2.6 per cent) a clear improvement and one (2.6 per cent) a smaller improvement, while the remaining four dogs showed no response after 11 to 60 days. Fifteen dogs (45.5 per cent) relapsed over the follow-up period of three to 191 days, but none of the dogs in the study exhibited any adverse effects.     

Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic–pituitary axis

Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported. However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect. The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary–adrenal axis in clinically normal dogs. Dogs were administered 5 mg/kg trilostane twice a day every day for 8 weeks (n = 8) or 16 weeks (n = 3). After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably. As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged. After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals. In addition, histological examinations revealed bilateral adrenal cortical hyperplasia. Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs. These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs. These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease.     

Bone allografts and adjuvant cisplatin for the treatment of canine appendicular osteosarcoma in 18 dogs

The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.     

Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The one- and two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.     

A retrospective study of clinical findings, treatment and outcome in 143 dogs with pericardial effusion

A retrospective study of 143 dogs with pericardial effusion is presented, including a statistical analysis of survival time. Cases were classified into those in which a mass was seen on echocardiography (echo-positive) and those in which no mass could be identified (echo-negative). Forty-four dogs were echo-positive and 99 were echo-negative. The median survival time (MST) was 1068 days for echo-negative dogs and 26 days for echo-positive dogs. Dogs with a history of collapse were more likely to present with a mass on echocardiography. Those presenting with collapse had an MST of 30 days compared with 605 days for those without collapse. Echo-negative dogs tended to present with ascites and generally had a larger volume of pericardial effusion. The median survival for dogs presenting with ascites was 605 days compared with 45 days for those without ascites. Among echo-negative dogs, 64 per cent had a relapse of their effusion. Subtotal pericardiectomy was performed in 31 echo-negative dogs. The procedure had a perioperative mortality of 13 per cent but provided a favourable long-term prognosis. Dogs undergoing pericardiectomy had a median survival of 1218 days compared with 532 days for those not undergoing surgery.     

Effects of farrowing crate floors on health and performance of piglets and sows

Three types of raised perforated floor were compared with floor-level concrete which had perforated flooring at the rear. Piglets on raised perforated floors grew faster (P less than 0.05) to 21 days than pigs on mainly solid floors (205 g/day and 198 g/day, respectively). The mortality in the first 21 days of all pigs born did not differ between raised (18.4 per cent) and mainly solid floors (18.7 per cent) and there were no effects of individual floor types on overall survival or on deaths due to crushing. The incidence of diarrhoea was not significantly less on raised than on solid floors (27 per cent and 34 per cent of litters, respectively) but antibiotic treatment time was shortened (0.9 days and 1.2 days, P less than 0.05). The incidence of splayleg was highest on fibreglass slats. Concrete floors caused most knee abrasions but the incidence of arthritis was unaffected. Approximately twice as many sows on mainly solid floors went off their feed or had a high rectal temperature compared with sows on raised perforated floors. No differences were observed between narrow or A-frame farrowing crates.     

Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection

The histological grade of 340 cutaneous mast cell tumours derived from 280 dogs was determined by an established histological grading system; 87 of the tumours (26 per cent) were well differentiated, 199 (59 per cent) were intermediately differentiated and 54 (16 per cent) were poorly differentiated. The one-year survival rates for the dogs with tumours of these three grades were significantly different (P = 0.0001), being 100 per cent, 92 per cent and 46 per cent, respectively. The median survival time for the dogs with poorly differentiated tumours was 278 days, significantly shorter than that for the dogs with either intermediately or well-differentiated tumours, which were both over 1300 days. Regrowth of the tumours was identified in 10 (19 per cent) of the dogs with poorly differentiated tumours, 12 (6 per cent) of the dogs with intermediately differentiated tumours and one of the dogs with well-differentiated tumours; only three of the tumours which regrew had initially had complete margins. The results suggest that wide surgical margins are not a prerequisite for a successful long-term outcome in dogs with well-differentiated cutaneous mast cell tumours.