Evaluation of satraplatin in dogs with spontaneously occurring malignant tumors.

BACKGROUND: Satraplatin is the 1st orally bioavailable platinum anticancer drug. OBJECTIVE: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor-bearing dogs, to identify the dose-limiting and other toxicities in dogs, and to record pharmacokinetics (PK). ANIMALS: Dogs with macro- or microscopic malignant neoplasia. METHODS: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. RESULTS: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty-three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m(2)/d for 5 days, repeated every 3-4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T(max) 1.8 (± 0.7) hours, C(max) 72 (± 26) ng/mL, area under concentration (AUC)(0-24 h) 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose-limiting and gastrointestinal toxicity was mild. CONCLUSIONS AND CLINICAL IMPORTANCE: Satraplatin was well tolerated in tumor-bearing dogs, thus warranting further investigation in a phase II trial.

Primary hyperaldosteronism in a dog with concurrent lymphoma.

An 11-year-old, male castrated English springer spaniel was presented for muscle weakness, lethargy and anorexia while undergoing treatment of Stage IV lymphoma. Persistent hypokalemia prompted multiple diagnostic tests. Serum aldosterone levels, surgical exploration and histopathology confirmed primary hyperaldosteronism. Hyperaldosteronism is a rarely reported endocrinopathy in the dog. This report describes a case in which immunohistochemistry was utilized to confirm the diagnosis of an aldosterone-secreting tumour.

Association between cancer chemotherapy and canine distemper virus, canine parvovirus, and rabies virus antibody titers in tumor-bearing dogs.

OBJECTIVE: To determine the association between cancer chemotherapy and serum canine distemper virus (CDV), canine parvovirus (CPV), and rabies virus antibody titers in tumor-bearing dogs. DESIGN: Prospective study. ANIMALS: 21 client-owned dogs with various malignancies and 16 client-owned dogs with lymphoma. PROCEDURE: In study A, serum antibody titers were measured by use of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) before and at least 1 month after initiation of chemotherapy. Baseline values were compared with values obtained from a control population of 122 healthy dogs seen for routine revaccination. Titers were considered protective at > or = 1:96 for CDV and > or = 1:80 for CPV. In study B, serum IgG titers were measured by use of immunofluorescent assay (CDV and CPV titers) and rapid fluorescent focus inhibition test (RFFIT, rabies titers) at baseline and again at weeks 5, 8, and 24 of a standard chemotherapy protocol for treatment of lymphoma. An IgG titer of > or = 1:50 was considered protective for CPV and CDV. An RFFIT titer of > or = 0.5 U/ml was considered protective for rabies virus. RESULTS: Significant changes were not detected in CDV, CPV, and rabies virus titers following chemotherapy in tumor-bearing dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that established immunity to CDV, CPV, and rabies virus from previous vaccination is not significantly compromised by standard chemotherapy used to treat tumor-bearing dogs.

Treatment of canine hemangiopericytomas with photodynamic therapy.

BACKGROUND AND OBJECTIVES: Canine hemangiopericytomas are a commonly occurring neoplasm with a clinical course of recurrence after surgical removal. This study sought to evaluate Photochlor (HPPH) photodynamic therapy (HPPH-PDT) as an adjuvant therapy to prevent recurrence of tumor after surgical removal. STUDY DESIGN/MATERIALS AND METHODS: Sixteen dogs with naturally occurring hemangiopericytomas were treated with surgical removal of the tumor followed by PDT using Photochlor as the photosensitizer. Photochlor was injected intravenously at a dose of 0.3 mg/kg. Forty-eight hours later the treatment consisted of surgical removal of the tumor followed by HPPH-PDT. RESULTS: Nine dogs (56%) had recurrence of tumor from 2 to 29 (median 9) months after treatment. These results are comparable or not as good as other forms of therapy. CONCLUSIONS: Photochlor photodynamic therapy applied after surgery appears to have no advantage over other forms of therapy in regards to preventing recurrence. Delayed wound healing and infections are problematic and make HPPH-PDT an undesirable addition to surgery for the treatment of this tumor type.

Immunomodulation therapy for feline leukemia virus infection.

Clinically ill feline leukemia virus (FeLV)-infected cats, treated with Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were compared with cats treated with saline (SAL). Nine cats received SPA/SAL, nine received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL. Twelve cats survived and completed the 100-week therapy. Significantly more owners of cats treated with SPA/SAL thought their cat's health improved during treatment compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison) or SPA/IFN (P=0.05, pair-wise comparison). No significant differences in body weight, temperature, hematocrit, red blood cell counts, mean corpuscular hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status, survival time, activity, or appetite scores were observed. No significant differences in the owners' subjective assessment of their cat's health following treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen. Therapy with SPA as a single agent results in the owners' subjective impression of improved health of their FeLV-infected cats.

Clinical assessment of a chemosensitivity assay as a treatment planning tool for dogs with cancer.

This study evaluated the clinical utility of a commercially available chemosensitivity assay. In the first part of the study, tumor tissues from dogs with various malignancies were tested, and the dogs were treated with a mitoxantrone/cyclophosphamide combination protocol. Tumor response was evaluated and compared to the predicted response. Assay results were not a significant predictor of clinical response to chemotherapy or of survival time. In the second part of the study, assay results were used to direct therapy in dogs with refractory lymphoma. There was no significant correlation (p equals 0.323) between predicted response and case outcome.

Assessment of five portable blood glucose meters, a point-of-care analyzer, and color test strips for measuring blood glucose concentration in dogs.

OBJECTIVE: To compare blood glucose concentrations obtained using a point-of-care (POC) analyzer, 5 portable blood glucose meters (PBGM), and a color reagent test strip with concentrations obtained using a reference method, and to compare glucose concentrations obtained using fresh blood samples in the PBGM with concentrations obtained using blood anticoagulated with lithium heparin. DESIGN: Case series. SAMPLE POPULATION: 110 blood samples from 34 dogs; glucose concentration of the samples ranged from 41 to 596 mg/dl. PROCEDURE: Logistic regression was used to compare blood glucose concentrations obtained with the various devices with reference method concentrations. Ease of use was evaluated subjectively. Percentage of times a clinical decision would have been altered if results of each of these methods had been used, rather than results of the reference method, was calculated. RESULTS: For 3 of the PBGM, blood glucose concentrations obtained with fresh blood were not significantly different from concentrations obtained with blood samples anticoagulated with lithium heparin. None of the devices provided results statistically equivalent to results of the reference method, but the POC analyzer was more accurate than the others. For some samples, reliance on results of the PBGM or the color test strip would have resulted in erroneous clinical decisions. CONCLUSIONS AND CLINICAL RELEVANCE: Although commercially available PBGM and color test strips provided blood glucose concentrations reasonably close to those obtained with reference methods, some devices were more accurate than others. Use of results from these devices could lead to erroneous clinical decisions in some cases.

Treatment of canine oral squamous cell carcinomas with photodynamic therapy.

Eleven dogs with naturally occurring oral squamous cell carcinomas were treated with photodynamic therapy (PDT) using Photochlor (HPPH) as the photosensitizer. The largest length of the tumours measured in a two-dimensional plane ranged from 0.9 to 6.8 cm. Seven of the tumours invaded underlying bone as determined by radiograph appearance. Photochlor was injected intravenously at a dose of 0.3 mg kg(-1). Forty-eight hours later the tumours were treated. Tumours with a surface to base depth of greater than 1 cm were surgically reduced to less than 1 cm. Irradiation with 665 nm light with an energy density of 100 J cm(-2) was administered. Eight dogs were considered cured with no tumour recurrence for at least 17 months after treatment. Local treatment of oral squamous cell carcinomas with PDT appears to give results similar to those obtained with surgical removal of large portions of the mandible or maxilla. The cosmetic results with PDT are superior to those of radical surgical removal. The new sensitizer, Photochlor, appears effective for oral squamous carcinomas with results similar to those reported for other sensitizers.

Effects of chromium supplementation on glucose tolerance in obese and nonobese cats.

OBJECTIVE: To determine effects of dietary supplementation with chromium (Cr) picolinate on health and response to i.v. glucose tolerance testing (IVGTT) in obese and nonobese cats. ANIMALS: 7 obese and 12 nonobese cats. PROCEDURE: 6 nonobese cats were untreated controls, whereas 6 different nonobese cats and 7 obese cats received oral administration of 100 microg Cr/d for 6 weeks. All cats were evaluated before and immediately after the treatment period by use of physical examination, CBC, serum biochemical analyses, and IVGTT. Calculated values included glucose half-life, coefficient of glucose disappearance, insulin peak response, insulinogenic index, and insulin secretion rate determined at various times after start of IVGTT. RESULTS: Adverse effects on cats' health were not observed during or after treatment, and significant changes in body weight, hematologic values, or most serum biochemical values were not detected. Serum potassium concentration decreased significantly after treatment in obese cats but was within reference range. Compared with nonobese cats, obese cats had significantly higher insulin peak response, insulinogenic index, and insulin secretion rate before and after treatment. Chromium supplementation did not alter responses to IVGTT in either treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation with 100 microg of Cr/d for 6 weeks is safe but does not affect glucose tolerance in obese or nonobese cats.

Recombinant human granulocyte colony-stimulating factor for treatment of puppies with neutropenia secondary to canine parvovirus infection.

OBJECTIVE: To determine the effect of treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for puppies with neutropenia secondary to canine parvovirus infection. DESIGN: Randomized controlled clinical trial. ANIMALS: 23 puppies. PROCEDURE: Diagnosis was confirmed by use of an ELISA for detection of canine parvovirus antigen in feces, and all puppies received standard treatment for parvoviral enteritis. All puppies had neutropenia (< 1,000 neutrophils/microliter) at the time of admission to the hospital or within 4 days afterward. Eleven puppies were treated with rhG-CSF daily until neutrophil count was > 1,500 cells/microliter; the remaining 12 puppies were not treated with rhG-CSF. RESULTS: We did not detect any significant differences between groups regarding duration of hospitalization, neutrophil count when neutropenia was first detected, lowest neutrophil count, or time until neutrophil count was > 1,500 cells/microliter. CLINICAL IMPLICATIONS: Results suggest that treatment with rhG-CSF may not be beneficial in puppies with neutropenia secondary to canine parvovirus infection.

Serum distemper virus and parvovirus antibody titers among dogs brought to a veterinary hospital for revaccination.

OBJECTIVE: To determine serum canine distemper virus (CDV) and canine parvovirus (CPV) antibody titers in healthy dogs brought to a veterinary hospital for revaccination. DESIGN: Case series. ANIMALS: 122 dogs. PROCEDURE: Serum antibody titers were measured by means of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) at the time dogs were brought to the hospital for revaccination. All dogs had been vaccinated between 271 and 1,665 days previously. Dogs were grouped by age, breed (purebred vs mixed breed), sex, and weight to determine whether these factors were associated with antibody titers. Serum CPV titers > or = 1:80 and serum CDV titers > or = 1:96 were considered protective. RESULTS: Breed, sex, and weight were not significantly associated with serum CPV and CDV titers. Age was significantly associated with CPV titer, with younger dogs having higher titers, but was not associated with CDV titer. Thirty-three of 122 (27%; 95% confidence interval, 19.0 to 34.9%) dogs had a less-than-protective CPV titer. Twenty-five of 117 (21%; 95% confidence interval, 13.6 to 28.4%) dogs had a less-than-protective CDV titer. CLINICAL IMPLICATIONS: Results suggest that, on the basis of serum antibody titers, the current practice of annual revaccination of dogs against CPV and CDV infection should be maintained. Measurement of antibody titers to determine whether revaccination is truly needed would seem justifiable in those dogs that have previously had an adverse reaction to vaccination.

Early protection of puppies against canine parvovirus: a comparison of two vaccines.

Client-owned puppies randomly were assigned to receive one of two commercially available polyvalent vaccines. The response to the parvovirus portion of each vaccine was evaluated by determining antibody titers by hemagglutination inhibition. Significant differences were found between titers produced by the vaccines. Puppies vaccinated with one of the products had a more desirable result as demonstrated by a protective antibody titer after the first vaccination (p of 0.005), a protective antibody titer at a younger age (p of 0.02), a protective antibody titer by 12 weeks of age (p of 0.001), and a protective antibody titer by 16 weeks of age (p of 0.05). Puppies vaccinated with this product also had significantly higher titers at each sampling after vaccination.

Vincristine therapy for mast cell tumors in dogs.

Twenty-seven dogs with naturally occurring mast cell tumors were treated with weekly i.v. injections of vincristine (0.75 mg/m2) for 4 treatments. Two dogs (7%) had a partial response. Nine dogs (32%) had treatment stopped prematurely because of toxicity or a perceived deterioration in their quality of life. We conclude that vincristine is ineffective as a sole treatment for measurable mast cell tumors in dogs and produces an undesirable number of adverse reactions.

Canine mandibular osteosarcoma: 51 cases (1980-1992).

Fifty-one dogs treated for mandibular osteosarcomas (OSs) were studied retrospectively. Treatments were partial mandibulectomy (n = 32); partial mandibulectomy and chemotherapy (n = 10); partial mandibulectomy and radiation therapy (n = 3); partial mandibulectomy, radiation therapy, and chemotherapy (n = 4); and radiation therapy alone (n = 2). The overall one-year survival rate was 59.3%. Dogs treated with surgery alone had a one-year survival rate of 71%, which is higher than the one-year survival rate for dogs with appendicular OSs treated with surgery alone (p of 0.001 or less; hazard ratio of 0.29). There was no apparent effect of various treatment modalities, nor institution where treatment was given, nor histological type. Histological score and, to a lesser extent, histological grade were predictive of survival outcome.

Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978-1992).

OBJECTIVE: To characterize the frequency, clinical signs, biologic behavior, and response to treatment of tumors of the ear canal in dogs and cats. DESIGN: Retrospective analysis of medical records. ANIMALS: Medical records of 81 dogs (48 malignant tumors, 33 benign tumors) and 64 cats (56 malignant tumors, 8 benign tumors). PROCEDURE: Data were analyzed for cats and dogs with malignant tumors, and risk factors were analyzed for their potential impact on survival time. RESULTS: Malignant tumor types most commonly reported included ceruminous gland adenocarcinoma, squamous cell carcinoma, and carcinoma of undetermined origin. Median survival time of dogs with malignant aural tumors was > 58 months, whereas that of cats was 11.7 months. A poor prognosis was indicated by extensive tumor involvement (dogs) and by neurologic signs at time of diagnosis, diagnosis of squamous cell carcinoma or carcinoma of undetermined origin, and invasion into lymphatics or blood vessels (cats). CLINICAL IMPLICATIONS: Malignant tumors of the ear canal in dogs and cats have a propensity for local invasion, but tend not to metastasize. Squamous cell carcinoma and carcinoma of undetermined origin were the most locally aggressive tumors. Malignant tumors of the ear canal are best managed by aggressive surgical excision. Radiotherapy may be useful when tumors cannot be completely removed.

Pharmacokinetics of pyropheophorbide-a-hexyl ether in the dog.

BACKGROUND AND OBJECTIVES: Pyropheophorbide-a-hexyl ether (HPPH) is a new compound being investigated for use as a photosensitizer for photodynamic therapy; however, the pharmacokinetics are not known for any of the target species likely to be treated with this drug. The objective of this study was to determine the pharmacokinetic parameters of this drug prior to institution of a clinical trial in canine patients with various cancers. STUDY DESIGN, MATERIALS AND METHODS: HPPH (0.3mg/kg i.v.) was administered to 12 dogs and blood samples were drawn at intervals for 24 hours and plasma HPPH concentrations were determined. Pharmacokinetic parameters were calculated for each dog. RESULTS: No evidence of toxicity was noted in any dog. The mean half-life was calculated to be 26.98 +/- 2.35 hrs. The mean clearance was 5.061 +/- 0.214 ml/hr/kg. The mean volume of distribution of the central compartment was 0.069 +/- 0.003 L/kg, and the mean steady state volume of distribution was 4.47 +/- 0.25 L/kg. CONCLUSION: The conclusion is that 0.3 mg/kg HPPH injected intravenously resulted in measurable plasma levels for 24 hrs, and resulted in no detectable adverse reactions.

Response of canine mast cell tumors to treatment with oral prednisone.

Twenty-five dogs with naturally occurring mast cell tumors were treated with daily oral prednisone (1 mg/kg) for 28 days. Five dogs (20%) had reduction in tumor volume and were considered responders. Four of these underwent partial remission and one underwent complete remission. Survival times for the five responders were 3, 5, 6, 7.5, and greater than 28 months, respectively. We therefore conclude that prednisone is effective in some canine mast cell tumors. Further studies are indicated to determine the most effective dose of prednisone, the appropriate duration of treatment, and the efficacy in more benign mast cell tumors, and in combination with other forms of therapy.

Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978-1988).

Long-term follow-up information pertaining to 162 dogs with appendicular osteosarcoma treated by amputation alone was collected from 17 veterinary institutions. The majority (72.5%) of dogs died or were euthanatized because of problems documented to be related to metastases. The first clinically apparent sites of metastasis were the lungs (60.8% of total), the skeleton (5.2%), or both (4.6%). A Kaplan-Meier survivorship distribution was plotted on the basis of available survival time data in all 162 dogs. The mean and median survival times were estimated to be 19.8 and 19.2 weeks, respectively, and the 1- and 2-year survival rates were estimated to be 11.5 and 2.0% respectively. Statistically significant relationships were not found between survival time and reporting institution, gender, site of primary tumor, whether the primary tumor was proximally or distally located, whether the primary tumor was located in the forelimb or hind limb, whether presurgical biopsy was performed, and whether death was tumor related. A significant (P less than 0.01) quadratic relationship was found between age and survival time. Survival time was longest in dogs 7 to 10 years old and was shorter in older and younger dogs.

Clinical, hematologic, and survival data from cats infected with feline immunodeficiency virus: 42 cases (1983-1988).

A retrospective study of stored feline serum samples was done to determine the infection rate of feline immunodeficiency virus in cats in central Missouri. Infected cats were compared with uninfected cats subjected to the same selection criteria on the basis of signalment, clinical signs, and CBC abnormalities. A significant incidence of virus infection was found in male cats. Neither age nor breed predilection could be identified. Infected cats were more likely to be anemic and leukopenic because of neutropenia. Cellulitis and neoplasia were more common in infected cats. A spectrum of disease severity was seen in infected cats ranging from no clinical signs to signs of severe chronic inflammatory disease. Infected cats were more likely to have clinical disease. Mean survival of infected cats was 24.4 months from the time of diagnosis.

Hepatic myelolipomas in a cat.

A 16-year-old spayed domestic cat was determined to have hepatic myelolipoma. Treatment consisted of incomplete surgical removal. Despite some tumor tissue remaining, the cat did well for 2 years, then died of an undiagnosed illness. Myelolipomas are tumors of extramedullary hematopoietic tissue, and have been reported uncommonly in cats. On the basis of the clinical course in people, myelolipomas were assumed to be benign in cats. The extended survival after incomplete surgical excision of the tumor in our cat supports this assumption.