Purpose: The immunotoxin BR96 sFv-PE40 is an effective antitumor agent against human breast and lung carcinoma xenografts in rodents. This study was designed to (a) determine the frequency with which canine carcinoma cells express Lewisy (Ley) antigen, thereby identifying canine carcinoma types suitable for the clinical evaluation of BR96 sFv-PE40, and (b) determine the safety and efficacy of BR96 sFv-PE40 in a canine model of spontaneously occurring cancers for investigation of targeted therapy. Experimental Design: Carcinoma tissue samples were obtained from client-owned dogs presented for medical care. The tissues were assessed for Ley antigen expression using immunohistochemical methods. Dogs with tumors expressing Ley antigen were offered enrollment in a clinical trial to receive twice-weekly infusions of 4 to 12 mg/m2 BR96 sFv-PE40. Clinical toxicity and response data were assessed at each treatment. Results: Twenty-two of 61 carcinomas evaluated were positive for Ley expression, including mammary, prostate, lung, and rectal carcinomas, and 12 dogs were enrolled in the clinical trial. The primary side effect was transient emesis. Partial responses or disease stabilization were noted in dogs with inflammatory mammary, bronchogenic, rectal, and tonsillar carcinoma. At least nine of the dogs developed antibodies to the immunotoxin after two to five infusions. Conclusions: Although development of anti-BR96 sFv-PE40 antibodies limited the long-term effectiveness of this immunotoxin in dogs, rapid clinical responses in several aggressive canine carcinomas suggest the immunotoxin has utility for treatment of certain naturally occurring tumors and that its clinical evaluation for treatment of similar human carcinomas is warranted.

OBJECTIVE:To determine whether hematologic and serum biochemical values for blood samples obtained from cats via vascular access ports (VAP) are comparable to those for samples obtained by direct venipuncture.DESIGN:Prospective study.ANIMALS:14 healthy cats.PROCEDURE:A VAP was surgically implanted in a jugular vein in each cat. Blood samples were obtained from the VAP and by direct venipuncture of the contralateral jugular vein 10 weeks after VAP placement. Results of hematologic and serum biochemical analyses were compared by use of a paired t-test. The Pvalue to reject the null hypothesis was adjusted to account for multiple comparisons by using the Bonferroni procedure in which the nominal P-to-reject value is divided by the number of comparisons (0.05/24 = 0.002).RESULTS:Paired samples (VAP and venipuncture) obtained 10 weeks after VAP placement were evaluated for each cat. Of the 24 measured analytes, only potassium, total protein, and albumin concentrations differed significantly (P< 0.001 for all 3) between VAP and venipuncture samples.CONCLUSIONS AND CLINICAL RELEVANCE:Results suggest that samples obtained from VAP are suitable for routine hematologic monitoring of feline cancer patients. Sample hemolysis may account for a slight increase in potassium, total protein, and albumin concentrations obtained from VAP samples. However, the values of variables most critical for monitoring of patients receiving chemotherapy (ie, mature neutrophil and platelet counts) are comparable. If proper techniques are used, VAP may be used for administration of chemotherapy as well as for blood collection in cats undergoing cancer treatment.

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.

OBJECTIVES To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin) -impregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse reactions. ANIMALS 6 healthy dogs. PROCEDURE Cisplatin (20 mg) was inserted into PMMA that was fashioned into cylinders and placed into subcutaneous tissue chambers overlying the thorax (treated site). An empty tissue chamber was placed over the opposite side (control site). Plasma samples were obtained for platinum determination before implantation, at 3, 6, and 12 hours after implantation on day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar days, tissue chamber fluid samples also were obtained for platinum determination. Complete blood count, serum urea nitrogen and creatinine concentration determinations, and urinalyses were performed on days 1, 2, 3, 7, 14, 21, and 29. Complete necropsy was performed at conclusion of the study. RESULTS Tissue chamber platinum concentrations at the treated site were significantly greater than plasma and control site tissue chamber concentrations on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 microg/ml), 6 (0.691 microg/ml), 12 (0.534 microg/ml), 24 (0.131 microg/ml), 48 (0.2 microg/ml), 72 (0.1 microg/ml), and 158 (0.014 microg/ml) hours was significantly greater than pretreatment values (0.0 microg/ml). Plasma platinum concentration 10 days after treatment (0.011 microg/ml) did not significantly differ from pretreatment values. Local or systemic adverse reactions were not apparent. CONCLUSIONS The route of cisplatin administration was safe. Greater concentration of platinum was released locally relative to plasma concentration for an extended period.

Thirteen dogs with histopathologically confirmed malignancies were treated with mitoxantrone and cyclophosphamide combination therapy. One to four doses were administered at 21-day intervals. Recombinant human granulocyte colony-stimulating factor was administered to ameliorate myelosuppression in dogs with neutrophil nadirs less than 1,000/microl. While the protocol appears to be safe for use in tumor-bearing dogs, an advantage over mitoxantrone single-agent protocols in terms of tumor response was not demonstrated in this initial pilot study.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) causes an initial increase in leukocyte counts:in small animals. A subsequent decline in leukocyte count is attributed to the development-dt neutralizing antibody to the rhG-CSF. According to the findings presented in this article, however, neutralizing antibodies against rhG-CSF did not develop in dogs or cats that received chemotherapy. Consequently, rhG-CSF might be useful for ameliorating chemotherapy-induced myelosuppression in small animals, thus permitting more aggressive chemotherapy protocols. Until further studies are completed, veterinarians should avoid administering rhG-CSF within 24 hours before or after chemotherapy. Giving the agent when neutrophil counts are less than,1000 cells/mu l is Sufficient to decrease the severity of myelosuppression. Short courses (three to six doses) may be sufficient to treat patients with severe myelosuppression. Long-term administration of rhG-CSF to normal dogs and cats might lead to the formation of antibodies to endogenous granolocyte colony-stimulating factor (G-CSF). Clients should be informed about the cost of therapy (approximately $0.72/mu g) versus the potential risks of withholding therapy.The; true-risks of withholding G-CSF therapy from neutropenic animals will not be clear until controlled randomized studies that involve tumor-bearing animals: are completed. the first part of this two-part article discusses the history of GL-CSF use in veterinary medicine and considers recommendations for administering G-CSF to chemotherapy patients. Part II will deal with the use of G-CSF in patients with infectious disease, such as canine parvovirus.

Case records of 32 cats with cutaneous mast cell tumors (CMCTs) were reviewed. Using the Patnaik system for grading canine mast cell tumors, the relationships between histopathological grade and patient survival time and tumor recurrence were examined. Tumor histopathological grade had no prognostic significance. One-, two-, and three-year tumor recurrence rates following surgical excision were 16%, 19%, and 13%, respectively. Incomplete excision was not associated with a higher rate of tumor recurrence.

A 4-month-old domestic shorthair cat was examined because of a maxillary gingival mass that had regrown following excisional biopsy. The kitten also had a history of persistently high blood glucose concentrations, despite 2 weeks of insulin treatment. Radiography revealed maxillary alveolar bone lysis and displacement of multiple teeth. Partial maxillectomy was performed to remove the mass, which histologically was a gingival vascular hamartoma. Hyperglycemia permanently resolved < 24 hours after mass removal. On the basis of the temporal relationship between mass removal and resolution of hyperglycemia, as well as the lack of evidence of any concurrent disease, hyperglycemia in this cat was considered to be a paraneoplastic syndrome.

A study was performed to determine the sensitivity and specificity of a commercially available microchip identification system approximately 1 year after implantation in dogs and cats. Thirty-three dogs and 16 cats in which a microchip had been implanted and 31 dogs and 18 cats in which a microchip had never been implanted were included in the study. In cats, sensitivity and specificity of microchip identification were 1.00. In dogs, sensitivity and specificity were 0.97 and 1.00, respectively. The chip had migrated in the 1 dog with a false-negative result, but the chip remained functional, and identification was established in this dog following closer physical examination and scanning.