Etoposide (VP-16)

A retrospective analysis was performed of the effect of VP-16 (etoposide) in the treatment of 13 dogs with lymphoma. Twelve dogs had achieved partial (two) and complete (ten) responses to combination chemotherapy, but all were out of remission at the time of the trial. One dog had not previously had chemotherapy. There was minimal response to VP-16 chemotherapy in the 13 dogs studied, and only two of 13 dogs had some response to treatment. For one dog, complete and partial remission durations were one and three months, respectively. In another dog, there was partial remission of eight days. There were no responses in the other 11 dogs. The most serious adverse reaction after administration of VP-16 was an acute pruritic cutaneous reaction that occurred in 11 of the 13 dogs, which may have been associated with the vehicle of VP-16, polysorbate 80. Results showed that VP-16 has minimal activity for treatment of dogs with lymphoma that have experienced relapses after treatment with other anti-cancer drugs. More trials are needed with higher dosages and the oral form of the drug, which does not contain polysorbate 80.     

Monthly application of 10 per cent moxidectin and 2{middle dot}5 per cent imidacloprid spot-on to prevent relapses in generalised demodicosis: a pilot study

Canine generalised demodicosis (GD) can be difficult to cure, with some dogs requiring life-long treatment. The aim of this pilot study was to evaluate the effectiveness of monthly 10 per cent moxidectin/2·5 per cent imidacloprid spot-on in maintaining long-term (12 months) clinical and parasitological remission in dogs with relapsing GD. Fourteen dogs were included: 10 with juvenile-onset GD (JOGD) and four with adult-onset GD (AOGD). All?dogs had been treated previously and relapsed (1-4 times). Each dog was treated again with either milbemycin oxime 2 mg/kg or ivermectin 400 μg/kg orally once daily, until two consecutive negative skin scrapings at one-month intervals (total 4-7 months of treatment). After treatment discontinuation, 10 per cent moxidectin/2·5 per cent imidacloprid spot-on was applied monthly for 12 months. Dogs were rechecked after 1, 2, 3, 6 and 12 months, and multiple skin scrapings were taken. Twelve dogs completed the study and were clinically normal and parasitologically negative at each recheck (four dogs with AOGD and eight with JOGD). One dog died suddenly for unrelated reasons, and one dog relapsed. Results of this pilot study suggest that monthly application of 10 per cent moxidectin/2·5 per cent imidacloprid spot-on may be effective as maintenance therapy in relapsing cases of GD.     

Intramedullary cisplatin chemotherapy: Experience in four dogs with osteosarcoma

Single-agent intramedullary cisplatin chemotherapy provided effective localised control in two of four dogs with advanced stage osteosarcoma unable to withstand an amputation or limb-sparing surgery. Complete remission of the local neoplasm was observed in one of the four dogs, partial remission of the local neoplasm in one dog and progressive disease in the other two. Limb function was preserved in one dog for seven months and that dog was found to be tumour-free when euthanased due to unrelated causes. These preliminary results warrant further investigation into the use of intramedullary cisplatin chemotherapy in the localised management of canine appendicular osteosarcoma. It is possible that this mode of treatment may be combined with other treatments to maximise the survival (ie, systemic control) in other dogs affected with appendicular osteosarcoma.     

Dexamethasone, melphalan, actinomycin D, cytosine arabinoside (DMAC) protocol for dogs with relapsed lymphoma

BACKGROUND: In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma. HYPOTHESIS: That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma. ANIMALS: Fifty-four dogs. RESULTS: Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2-467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog). CONCLUSIONS AND CLINICAL IMPORTANCE: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated.     

Temporary remission of disseminated paecilomycosis in a German shepherd dog treated with ketoconazole

Disseminated mycosis caused by Paecilomyces varioti in a female German shepherd dog presented with chronic forelimb lameness is described. Radiographs of the swollen carpal joint revealed geographic lysis of the radial epiphysis. Diagnosis was based on cytological demonstration of fungal hyphae and chlamydiospores, as well as fungal culture of fluid obtained by arthrocentesis. Temporary remission was characterised by markedly improved clinical signs and laboratory parameters, following treatment with ketoconazole. The dog was euthanased 9 months after the initial diagnosis, following the diagnosis of multifocal discospondylitis. This appears to be the longest described period of temporary remission obtained with treatment in dogs with paecilomycosis. Clinical, clinicopathological and necropsy findings of this disease in another German shepherd dog are briefly described.     

Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987-1998)

OBJECTIVE: To determine the efficacy (durations of remission and survival) of an alternating-day radiation protocol for incompletely excised histologic grade-III solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS: 31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol) was delivered to an area bordered by margins > or = 3 cm around the surgical scar and to the associated local-regional lymph nodes. Dogs were not given chemotherapeutic agents concurrently or after radiation. Information on signalment, duration of remission, and survival time was obtained from medical records. RESULTS: Median and mean durations of remission were 27.7 and 17.0 months, respectively (range, 1 to 47 months). Median and mean durations of survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with tumors located on the skin of the pinna, perineum, and prepuce had a median duration of remission greater than dogs with tumors located at other sites (27.7 and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months, respectively). The remission rate was 65% and survival rate was 71% at 1 year after treatment. Sixteen dogs that were euthanatized had complications associated with local-regional tumor progression. Systemic metastases to liver, spleen, intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Without further treatment, incompletely excised grade-III mast cell tumors have high local-regional recurrence; local-regional treatment with radiation may effectively be used to manage many such tumors.     

Treatment of five haemodynamically stable dogs with immune‐mediated thrombocytopenia using mycophenolate mofetil as single agent

Five dogs were presumptively diagnosed with immune‐mediated thrombocytopenia. As they had all been chronically treated with non‐steroidal anti‐inflammatory drugs, administration of immunosuppressive doses of corticosteroids was considered contraindicated. Non‐steroidal anti‐inflammatory drugs were temporarily discontinued in all the dogs and mycophenolate mofetil was introduced as first‐line single immunomodulatory therapy. This treatment protocol resulted in complete remission of immune‐mediated thrombocytopenia in all the dogs, and mycophenolate mofetil was discontinued after several months of therapy in four of the five dogs with no relapses, even when non‐steroidal anti‐inflammatory drug administration was resumed. The remaining dog required continued mycophenolate mofetil therapy to avoid relapse. One dog experienced diarrhoea, and another dog had diarrhoea and decreased appetite .     

Intranasal melanoma treated with radiation therapy in three dogs

Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.     

Weekly administration of low-dose doxorubicin for treatment of malignant lymphoma in dogs

Nine dogs with intermediate- or high-grade lymphoma were prospectively entered into a protocol to be given a total of 15 weekly doses of doxorubicin (10 mg/m2 of body surface, IV) in an attempt to eliminate all clinical evidence of neoplasia, with minimal risk of drug toxicity. Eight of these dogs did not complete the protocol because of progression of the disease. The median number of doses administered to dogs that developed progressive disease before the regimen was completed was 5 (range, 2 to 9). Seven dogs achieved partial (n = 5) or complete (n = 2) remission, with median duration of 14 days (range, 7 to 231 days). The dog that was given all 15 weekly treatments remained in complete remission for 231 days. Complete remission that lasted for 14 days was observed in another dog. Toxicosis developed in 3 dogs; signs of toxicosis were generally mild and included colitis (n = 1), vomiting (n = 1), neutropenia (n = 1), and lethargy (n = 1). The lowest neutrophil count (1,876 cells/microliter) was seen in one dog after 7 doses of doxorubicin were given. Doxorubicin at dosage of 10 mg/m2/wk appears to be safe, but is generally ineffective for treatment of lymphoma.     

Treatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia

Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long‐term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long‐term remission (median 21.1 months, [3.0‐44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long‐term remission, of which one needed on‐going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on‐going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long‐term compared to dogs treated with an antibiotic. Furthermore, the need for long‐term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second‐line treatments.     

Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs

OBJECTIVE: To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs. DESIGN: Prospective case series. ANIMALS: 17 dogs with measurable oral squamous cell carcinoma. PROCEDURE: Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died. RESULTS: One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.     

Focal metatarsal fistulae syndrome affecting a greyhound dog successfully treated with topical 0.1% tacrolimus ointment

Metatarsal fistulation is an uncommon cutaneous condition reported almost exclusively in German shepherd dogs and their cross‐breeds. To the best of the authors’ knowledge this is the first reported case of focal metatarsal fistulae syndrome affecting a greyhound. Remission was obtained within 6 weeks of commencing treatment using compounded 0.1% tacrolimus ointment twice daily and the dog remained stable for another 6 months with twice weekly application before treatment was discontinued. The dog remained in remission at the time of writing, which is 1 year after treatment withdrawal.     

Single-Drug Chemotherapy of Canine Transmissible Venereal Tumor With Cyclophosphamide, Methotrexate, or Vincristine

During a 21-month period, 48 dogs with spontaneous canine transmissible venereal tumor (clinical stage, T1-T3) were presented to the Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria, and were divided into one control and four treatment groups to test the efficacy of single-agent chemotherapeutic drugs. The dogs were not randomly assigned to groups because each chemotherapeutic agent was not continuously available during the test period. Group I consisted of four dogs that received oral cyclophosphamide (50 mg/M2 body surface area [BSA]) on the first four days for six weeks. No therapeutic response was noted in any of the four dogs. Group II consisted of ten dogs that received intravenous (IV) cyclophosphamide (50 mg/M2 BSA) for four consecutive days per week for six weeks. Two of the ten had a partial remission. Group III consisted of eight dogs that received oral methotrexate (2.5 mg/M2 BSA) every other day for six weeks. No therapeutic response was noted in any of the eight dogs. Group IV consisted of 20 dogs that were administered IV vincristine sulfate (0.5 mg/M2 BSA) weekly until a response was noted. Complete remission occurred in each of the 20 dogs. One dog had recurrence within 12 months. Group V was the untreated control group, consisting of six dogs among which no spontaneous remission was seen. Instead, tumor progression was noted. Adverse responses to medication, anorexia, vomiting, diarrhea, and weight loss were seen only with dogs treated with cyclophosphamide and methotrexate.     

Azathioprine therapy for acquired myasthenia gravis in five dogs.

Five dogs with acquired myasthenia gravis (MG), verified via positive serum acetylcholine (ACh) receptor antibody concentrations, were treated with a drug protocol including azathioprine (AZA). Four of the five dogs were concurrently treated with pyridostigmine. Azathioprine was used as the sole immunosuppressive agent in four dogs. One dog was temporarily treated with a combination of an immunosuppressive dose of prednisone and AZA, then maintained on AZA as the sole immunosuppressive drug. Three patients experienced complete remission of clinical signs within three months of therapy. In the four dogs for which follow-up serum ACh receptor antibody concentrations were available, initial versus final concentrations decreased substantially (81%), coincident with clinical improvement. One dog died suddenly due to a suspected myasthenic crisis before attaining the target dose of AZA. Two of the four surviving dogs were euthanized approximately one and seven years after diagnosis. One of these two dogs was euthanized because of a rib osteosarcoma, and the other dog was euthanized because of paraparesis of undetermined cause. The remaining two dogs were alive and doing well at the time of final follow-up evaluation, approximately six months and one year after diagnosis. The use of AZA as a therapeutic agent for acquired canine MG has not been investigated. The cases presented in this report suggest a potentially important role for AZA in the treatment of acquired MG in dogs.     

Thoracic, Abdominal and Vertebral Actinomycosis

The clinical, laboratory, radiographic, and histologic features and the response to therapy in three dogs with actinomycosis are reported. One dog (dog 1) had a 12-cm nonresectable mass extending from the ventrolateral chest wall into the left ventricular myocardium. Another dog (dog 2) had a diffuse peritonitis with "sulfur granules" and two large masses. One of these masses was nonresectable involving adjacent abdominal structures. A third dog (dog 3) had a subvertebral mass at T1-3 producing quadraplegia. Two dogs had periosteal reactions involving adjacent sternebrae (dog 1) or ribs and vertebral bodies (dog 3) that are characteristic of Actinomyces spp infections. In dogs 1 and 2 the diagnosis was based on the morphologic and tinctorial properties of free sulfur granules and/or tissue granules. Culture results were variable. Tissue from dog 1 yielded no growth, while polymicrobial infections, which included Actinomyces spp, were identified in dogs 2 and 3. Actinomyces odontolyticus was isolated from dog 3. Although the actinomycotic granulomas were either not excised or only partially excised from dogs 1 and 2, both animals were cured by the oral administration of high doses of penicillin G for 19 and 6 months, respectively. Dog 3 responded dramatically to the same antibiotic therapy given for 5 months. However, within 4 months of discontinuing treatment an abscess and draining fistulous tracts developed in the left axillary region. Two surgical fistulectomies and additional penicillin therapy were required to cure this animal. These cases and the current veterinary and human literature on actinomycosis are used to propose a rational approach to the treatment of actinomycosis in the dog.     

FC-20 Efficacy of griseofulvin for juvenile cellulitis in dogs

Medical records of 97 dogs with pemphigus foliaceus were evaluated. The average age of onset was 6.3 years (range 0.5–16 years). Crusts were the most common lesions in 79 dogs; pustules were observed in 36 dogs. No gender predisposition was identified. The trunk was the most commonly involved area (51 dogs), followed by the inner pinnae (46), dorsal muzzle (37), footpads (32), periocular area (26), outer pinnae (23) and planum nasale (23). Facial involvement only was noted in 15 dogs. Of the 48 dogs in which cytology was recorded, concurrent infections were identified in 32 dogs, acantholytic cells were seen in 37 dogs, numerous neutrophils in 35 dogs, and numerous eosinophils in eight cases. Final control of the disease was achieved with: glucocorticoids (24 dogs); azathioprine (9); chlorambucil (1); aurothioglucose (1); a combination of glucocorticoids and azathioprine (31); glucocorticoids and aurothioglucose (2); tetracycline/doxycycline and niacinamide (8); prednisolone, tetracycline and niacinamide (1); fatty acid supplementation (2); and tacrolimus (1). One dog was completely tapered off drugs and stayed in remission. Average time to improvement was 6 weeks, and average time to remission was 9.3 months. Forty-three dogs were followed for <12 months, and 12 of these were euthanized: eight for other diseases and four due to a lack of response or adverse effects of treatment. In 54 dogs, the follow up was >12 months; four of these dogs were euthanized (one due to an unrelated cause, one due to neoplastic disease and two related to pemphigus foliaceus).
Funding: Self-funded.     

FC‐18 Pemphigus foliaceus in 97 dogs

Medical records of 97 dogs with pemphigus foliaceus were evaluated. The average age of onset was 6.3 years (range 0.5–16 years). Crusts were the most common lesions in 79 dogs; pustules were observed in 36 dogs. No gender predisposition was identified. The trunk was the most commonly involved area (51 dogs), followed by the inner pinnae (46), dorsal muzzle (37), footpads (32), periocular area (26), outer pinnae (23) and planum nasale (23). Facial involvement only was noted in 15 dogs. Of the 48 dogs in which cytology was recorded, concurrent infections were identified in 32 dogs, acantholytic cells were seen in 37 dogs, numerous neutrophils in 35 dogs, and numerous eosinophils in eight cases. Final control of the disease was achieved with: glucocorticoids (24 dogs); azathioprine (9); chlorambucil (1); aurothioglucose (1); a combination of glucocorticoids and azathioprine (31); glucocorticoids and aurothioglucose (2); tetracycline/doxycycline and niacinamide (8); prednisolone, tetracycline and niacinamide (1); fatty acid supplementation (2); and tacrolimus (1). One dog was completely tapered off drugs and stayed in remission. Average time to improvement was 6 weeks, and average time to remission was 9.3 months. Forty‐three dogs were followed for <12 months, and 12 of these were euthanized: eight for other diseases and four due to a lack of response or adverse effects of treatment. In 54 dogs, the follow up was >12 months; four of these dogs were euthanized (one due to an unrelated cause, one due to neoplastic disease and two related to pemphigus foliaceus). Funding: Self‐funded.     

Treatment of Relapsed Canine Lymphoma With Doxorubicin and Dacarbazine

Fifteen dogs with relapsed lymphoma were treated with doxorubicin and dacarbazine (ADIC) to reinduce remission. All the dogs' lymphomas had become resistant to prior therapy with doxorubicin alone. Five of the 15 dogs had a complete response to the first treatment with ADIC, and three had partial responses. Of the eight dogs receiving a second cycle, two had complete responses, and one had a partial response. One dog that received a third ADIC treatment no longer responded. The median survival time from the first ADIC treatment for all dogs was 45 days (range, 18-241 days). The five dogs having complete responses to the first ADIC treatment had a median survival time of 105 days (range, 45-241 days) after this treatment. Toxicity due to ADIC treatment was acceptable and did not exceed that seen when doxorubicin was given as a single agent. The treatment resulted in severe neutropenia in three dogs. One dog died due to neutropenic sepsis. Vomiting, diarrhea, and anorexia occurred, but were tolerable, resulting in hospitalization in only one instance. ADIC is apparently a useful chemotherapeutic combination to reinduce remission in some dogs with relapsed lymphoma.     

A Combination Chemotherapy Protocol (VELCAP-L) for Dogs with Lymphoma

Ninety-eight dogs with lymphoma treated with a 5-drug combination chemotherapy regimen (vincristine, L-asparaginase. cyclophosphamide, doxorubicin, prednisone [VELCAP-L]) were evaluated for pretreatment characteristics predictive for response and remission duration. The complete remission rate was 69%, with a median remission duration of 55 weeks. Dogs with advanced stage of disease, constitutional signs, dogs that were older, and dogs that were dyspneic were less likely to achieve remission. Once in remission, small dogs and dogs without pretreatment thrombocytopenia were likely to have longer remission duration. Toxicoses were frequent, but rarely fatal, and no predictitive factors were found for a dog developing toxicoses. VELCAP-L is an effective treatment for dogs in stage I-III lymphoma, particularly in young, small animals.