Epirubicin in the treatment of canine histiocytic sarcoma: sequential,alternating and rescue chemotherapy

The aims of this study were to report treatment outcomes for dogs with histiocytic sarcoma (HS) treated with both lomustine and epirubicin, and to report response rates to epirubicin as a rescue therapy in dogs previously treated with lomustine. Medical records of dogs with a diagnosis of HS that were treated with both lomustine and epirubicin were retrospectively evaluated. Of 29 dogs receiving epirubicin alternating with, or subsequent to lomustine treatment, including in a rescue setting, response to epirubicin could be assessed in 20 with an overall response rate (ORR) of 29% and biological response rate (BRR) of 71%. Median time to progression (TTP) in 12 of these 20 dogs in which it was assessable was 69 days (range: 40‐125 days). For dogs treated in the rescue setting epirubicin specific ORR was 19% and BRR 63%. Median TTP in the 9 of these 16 dogs in which it was assessable was 62 days (range: 40‐125 days). Median survival time for all dogs treated with both epirubicin and lomustine was 185 days (range: 27‐500 days). Some dogs with HS respond to epirubicin and dogs treated with combinations of epirubicin and lomustine have modestly improved survival times compared with single agent studies, and similar to dogs with HS treated with alternating lomustine and doxorubicin. Single agent epirubicin is also a valid short term rescue therapy for canine HS.     

Systematic Review of Brain Tumor Treatment in Dogs

Intracranial neoplasia is commonly diagnosed in dogs and can be treated by a variety of methods, but formal comparisons of treatment efficacy are currently unavailable. This review was undertaken to summarize the current state of knowledge regarding outcome after the treatment of intracranial masses in dogs, with the aim of defining optimal recommendations for owners. This review summarizes data from 794 cases in 22 previously published reports and follows PRISMA guidelines for systematic review. A Pubmed search was used to identify suitable articles. These then were analyzed for quality and interstudy variability of inclusion and exclusion criteria and the outcome data extracted for summary in graphs and tables. There was a high degree of heterogeneity among studies with respect to inclusion and exclusion criteria, definition of survival periods, and cases lost to follow‐up making comparisons among modalities troublesome. There is a need for standardized design and reporting of outcomes of treatment for brain tumors in dogs. The available data do not support lomustine as an effective treatment, but also do not show a clear difference in outcome between radiotherapy and surgery for those cases in which the choice is available.     

Clinicopathological features and outcome for dogs with mast cell tumors and bone marrow involvement

BACKGROUND: Mast cell tumors (MCTs) with bone marrow (BM) involvement are poorly documented in dogs and are associated with a poor prognosis. Successful treatment strategies have not been described. HYPOTHESIS: Clinicopathologic findings of affected dogs are not specific. Administration of lomustine or imatinib is beneficial. ANIMALS: Fourteen dogs with MCT and BM involvement. METHODS: Clinical and laboratory evaluations were performed in each dog on admission and during follow-up. All dogs received prednisone. Additionally, 8 dogs received lomustine and 3 dogs received imatinib. Imatinib was administered if tumor-associated tyrosine kinase KIT was aberrant. RESULTS: On admission, 11 dogs had a single cutaneous nodule and 3 dogs had multiple nodules. Involvement of regional lymph nodes, liver, or spleen was observed in each dog. BM infiltration with mast cells (MCs) was observed in all dogs. On CBC, nonregenerative anemia, leukopenia, or thrombocytopenia was common. Four dogs had circulating MCs. Increased alkaline phosphatase or alanine transferase activity was observed in 12 and 10 dogs, respectively. Treatment with lomustine induced partial remission in 1 of 8 dogs. Median survival time was 43 days (range, 14-57). Dogs on imatinib experienced complete remission. Two dogs survived for 117 and 159 days, and the third was alive after 75 days. Dogs treated symptomatically did not improve and were euthanized after 1, 14, and 32 days. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of clinical and laboratory evaluation helps in identifying dogs with MCT and BM infiltration. Administration of lomustine is not helpful in affected dogs. The beneficial effect of imatinib warrants further investigation.     

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first‐line adjuvant anthracycline (AC) or metronomic (MC)‐based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC‐ or MC‐based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety‐three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47‐3352) and the overall median TTP was 185 days (range 37‐1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47‐3352 days), 338 days for the AMC group (range 79‐1623 days) and 225 days for the MC group (range 57‐911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings.     

Evaluation of intracavitary mitoxantrone and carboplatin for treatment of carcinomatosis,sarcomatosis and mesothelioma,with or without malignant effusions: A retrospective analysis of 12 cases (1997–2002)*

Carcinomatosis, sarcomatosis and mesothelioma, with or without malignant effusions, are difficult to treat and generally carry a poor prognosis. The purpose of this study was two‐fold; first, to determine the prognosis for dogs with carcinomatosis, sarcomatosis, or mesothelioma, with or without malignant effusions; second, to evaluate the safety and efficacy of treatment with intracavitary (IC) carboplatin and mitoxantrone in dogs with these syndromes. Nineteen dogs were evaluated. Seven were untreated and 12 were treated with IC chemotherapy (mitoxantrone and/or carboplatin), and multiple factors were analysed for significance with respect to survival time. The median survival time (MST) for untreated dogs was 25 days, whereas the MST for treated dogs was 332 days (Log Rank, P < 0.0001). Treatment with IC chemotherapy was well tolerated. This study suggests that IC chemotherapy with mitoxantrone and/or carboplatin is an effective treatment for dogs with carcinomatosis, sarcomatosis or mesothelioma, with or without malignant effusion.     

Hypofractionated Radiation Therapy of Brain Masses in Dogs: A Retrospective Analysis of Survival of 83 Cases (1991–1996)

There are few reports of radiation treatment for brain tumors in dogs, and the optimal treatment protocol has yet to be established. We completed a retrospective analysis of the survival times of a series of 83 dogs with intracranial masses that were treated by hypofractionated megavoltage radiation therapy. A total tumor dose of 38 Gray was given over 5 weeks as once weekly fractions via 3 perpendicular portals. The median survival time from the start of radiotherapy for the whole cohort was 43.7 weeks (range, 0.1-172 weeks). Extra-axial masses had a better survival time (49.7 weeks) than did other intracranial masses (intra-axial, 40.4 weeks; pituitary, 21.0 weeks). Delayed radiation toxicity was suspected as the cause of death or reason for euthanasia in 12 dogs. The hypofractionated radiation protocol resulted in survival times similar to those obtained using more conventional multifractionated regimens, and this protocol may be a useful, less intensive alternative treatment for brain tumors in dogs.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

Recurrence rate of presumed thoracolumbar intervertebral disc disease in ambulatory dogs with spinal hyperpathia treated with anti-inflammatory drugs: 78 cases (1997–2000)

Objective: To determine the recurrence rate of clinical signs in dogs with spinal hyperpathia and mild neurological deficits due to presumed Hansen Type 1 thoracolumbar intervertebral disc disease (IVDD) that were managed medically with anti‐inflammatory agents, and to compare the recurrence rates between dogs treated with corticosteroids and those treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). Design: Retrospective study. Setting: Private veterinary emergency clinic in a large metropolitan area. Animals, interventions, and measurements: Medical records were used to ascertain study eligibility, record patient signalment and condition severity, and document medical treatment regimen. Each dog was assigned a severity score: (1) spinal hyperpathia with no neurological deficits, (2) spinal hyperpathia with conscious proprioceptive deficits only, or (3) spinal hyperpathia with ataxia but still retaining ambulatory motor function. Owners of 78 dogs weighing less than 16 kg presented from 1997 through 2000 were sent a questionnaire to determine recurrence rate. Main results: All dogs recovered from the initial episode; 39 experienced recurrence and 39 did not. There was no statistically significant relationship between gender, age, or severity score and recurrence rate. Dogs treated with NSAIDs or methylprednisolone sodium succinate (MPSS) were less likely to experience recurrence than dogs treated with corticosteroids other than MPSS. Conclusion: A 50% recurrence of presumed IVDD occurred in this population of dogs after treatment with NSAIDs or corticosteroids. Those treated with NSAIDs or MPSS were less likely to experience a recurrence.     

A retrospective review of treatment and response of high‐risk mast cell tumours in dogs

This retrospective case series evaluates survival outcome of 94 dogs with high metastatic risk mast cell tumours (MCT). Patients were treated with a cytotoxic chemotherapy protocol or the tyrosine kinase inhibitor masitinib, in the presence of gross disease or as an adjunct to surgical resection of the primary tumour. In patients presenting with metastatic disease, surgical resection of the primary tumour with adjunctive therapy with any chemotherapy incurred a significant survival advantage [median survival time (MST): 278 days] compared to patients receiving chemotherapy without surgical excision of the primary tumour (MST: 91 days, P < 0.0001). Patients with a surgically excised Patnaik grade II tumour and high Ki‐67 in the absence of metastatic disease treated with vinblastine and prednisolone showed a significantly longer survival (MST: 1946 days) than those treated with masitinib (MST: 369 days, P = 0.0037). Further prospective case‐controlled clinical trials of high‐risk MCTs are required to make precise evidence‐based treatment decisions for individual patients.     

Electrochemotherapy in treatment of canine oral non‐tonsillar squamous cell carcinoma. A case series report

Non‐tonsillar squamous cell carcinoma (ntSCC) is a common and locally aggressive oral tumour in dogs. The treatments of choice are currently surgery and radiotherapy. Electrochemotherapy (ECT) is a local ablative anti‐tumour technique using electric pulses to enhance the intracellular diffusion of cytotoxic drugs. The aim was to retrospectively evaluate the outcome of patients with oral ntSCC treated with ECT. Twelve dogs with ntSCC were retrospectively enrolled. ECT was combined with IV bleomycin (15 000 UI/m²) alone in 11 cases and post‐surgery in 1. Parameters considered were: tumour site and size, electroporation parameters, response rate (complete remission [CR], partial remission [PR]), median survival time (MST), recurrence rate (RR), median disease‐free interval (DFI) and treatment toxicity (6‐point scale). Median tumour size was 1.65 cm (range 0.3‐8.0 cm) and the response rate was 90.9% (10/11; 8 CR and 2 PR). Two dogs underwent a second ECT. MST for dogs dead with tumour (n = 2) was 110 days and for dogs dead without tumour (n = 3) was 831 days. Among five surviving dogs, one experienced tumour recurrence and four were in CR. Results from two dogs were analysed separately. Overall RR was 27.3%. DFI and MST for dogs with recurrence were 50 and 115 days, respectively. Treatment toxicity was very low. We noticed that all dogs with tumours smaller than 1‐2 cm achieved CR without recurrence suggesting a favourable prognosis when using ECT. ECT for canine ntSCC could be considered a valid treatment option especially for smaller tumours, but a larger caseload would be needed to confirm this statement.     

Colorectal adenocarcinoma in dogs: 78 cases (1973-1984)

Colorectal adenocarcinoma was diagnosed in 78 dogs. Clinical signs in all 78 dogs included tenesmus, hematochezia, and dyschezia; most of the dogs had clinical signs less than or equal to 12 weeks before examination. Ultimately, most dogs were euthanatized because of the severity of clinical signs. Proctoscopy and colonoscopy were essential for complete assessment of extent of disease. Tumors were classified by gross appearance and included single, pedunculated masses, 2 or more nodular masses, and annular or intraluminal masses. In dogs in which survival time was compared with location and gross appearance of the tumor, dogs with annular masses had the shortest mean survival time (1.6 months), and dogs with single, pedunculated, polypoid tumors had the longest mean survival time (32 months). The rectum was a more common site than the colon, with 48.2% of the tumors developing in the middle portion of the rectum. Six different modes of surgical treatment were used, depending on the location and type of mass. Dogs that did not have surgical treatment had a mean survival time of 15 months. Mean survival time in the surgically treated dogs varied slightly according to mode of treatment; they survived 7 to 9 months longer than the untreated dogs. Dogs that underwent cryosurgery and local excision had the longest survival times (24 and 22 months, respectively). Statistical analysis disclosed a significantly longer survival time for dogs treated by excision or cryosurgery, as opposed to dogs undergoing biopsy only (P = 0.001). Statistical difference in survival times was not found between dogs that had mass excision and those that had cryosurgery.     

Successful management of 3 dogs with colonic pythiosis using itraconzaole,terbinafine, and prednisone

Gastrointestinal (GI) pythiosis is a severe and often fatal disease in dogs that traditionally has been poorly responsive to medical treatment. Although aggressive surgical resection with wide margins is the most consistently effective treatment, lesion location and extent often preclude complete resection. Recently, it has been suggested that the addition of anti‐inflammatory doses of corticosteroids may improve outcome in dogs with nonresectable GI pythiosis. This report describes 3 dogs with colonic pythiosis in which complete resolution of clinical signs, regression of colonic masses, and progressive decreases in serological titers were observed after treatment with itraconazole, terbinafine, and corticosteroids. This treatment protocol represents a promising treatment for dogs with GI pythiosis in which surgical intervention is not feasible.     

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 .     

Canine multicentric lymphoma 2: Comparison of response to two chemothera-peutic protocols

This paper describes the chemotherapeutic response of 90 cases of canine multicentric lymphoma. All the dogs were treated with a combination protocol using cyclophosphamide, vincristine and prednisolone. Forty-seven dogs received additional intravenous cytosine arabinoside on the first four days of treatment. Eighty-eight per cent of all cases had shown either a complete or partial response to this treatment at six weeks from the start of treatment and the overall mean survival time was 37 weeks (SD = 35.8). There was no significant difference in response or survival rates between the two treatment groups. The age and sex of the patient, the clinical stage of the disease and previous treatment with corticosteroids were all analysed to determine whether these parameters were of prognostic significance. Those dogs in clinical stages 4 and 5 carried a worse prognosis than those in stages 1 to 3. Previous treatment with corticosteroids adversely affected both tumour response and patient survival rates.     

Xenogeneic murine tyrosinase DNA vaccine for malignant melanoma of the digit of dogs

Background: Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. Objectives/Hypothesis: Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Animals: Fifty‐eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Methods: Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Results: Overall median survival time (MST) for dogs treated with loco‐regional control and xenogeneic DNA vaccine was 476 days with a 1‐year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P < .0001). Forty‐eight percent of the dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I–IV dogs surviving >952, >1,093, 321, and 76 days, respectively. Conclusions and Clinical Importance: The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system.     

A Retrospective Study of Multi‐agent Chemotherapy including either Cyclophosphamide or Lomustine as Initial Therapy for Canine High‐grade T‐cell Lymphoma (2011‐2017)

Multi‐agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first‐line chemotherapy to treatment‐naïve canine lymphoma patients with measurable, high grade T‐cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi‐agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild‐to‐moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression‐free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine‐based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first‐line, multi‐agent therapy for patients with HGTCL.     

Doxorubicin chemotherapy for presumptive cardiac hemangiosarcoma in dogs†

Sixty‐four dogs were treated with single‐agent doxorubicin (DOX) for presumptive cardiac hemangiosarcoma (cHSA). The objective response rate (CR + PR) was 41%, and the biologic response rate (CR + PR + SD), or clinical benefit, was 68%. The median progression‐free survival (PFS) for treated dogs was 66 days. The median survival time (MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs (P = 0.0001). Biologic response was significantly associated with improved PFS (P < 0.0001) and OS (P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA.     

Pathologic fracture in dogs with suspected or confirmed osteosarcoma

Objective: To evaluate clinical presentation of pathologic fractures associated with suspected or confirmed osteosarcoma in dogs and to assess treatment and survival times. Study design: Case series. Animals: Dogs (n=25) appendicular pathologic fracture. Methods: Medical records (January 1997–May 2008) of dogs with pathologic fracture associated with a suspected or confirmed osteosarcoma were reviewed. Dogs were included if they had radiographic evidence of a pathologic fracture and a presumptive or definitive diagnosis of osteosarcoma. Radiographic details, histopathology, and/or cytology findings were recorded. Overall median survival time (MST) and MST of treated dogs were calculated. Age, sex, breed, and other concurrent treatment were evaluated. Results: Rottweilers, Irish Wolfhounds, and Greyhounds were the most common breeds represented. Most dogs had minor trauma and 60% had lameness preceding the fracture. Most commonly, fractures were nondisplaced with minimal comminution. None of the dogs had radiographic evidence of pulmonary metastases at admission. Immediate (13 dogs; 52%) and delayed (4; 16%) euthanasia were performed. One dog was not treated and died 90 days after diagnosis. Three dogs (12%) were treated by amputation alone, 1 (4%) with amputation and chemotherapy, and 3 (12%) with internal fixation using an interlocking nail. Overall MST was 1 day (range, 0–623 days) and MST of treated dogs was 406.5 days. Histologic confirmation of osteosarcoma was available in all treated dogs and 6 euthanatized dogs. Conclusions: Treatment of pathologic fracture associated with presumptive osteosarcoma should be considered as an option to amputation or euthanasia if owners desire other options.