Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study.

Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low-dose metronomic and/or anti-angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose-finding clinical trial assumed an open-label 3 + 3 cohort design. Client-owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg-1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m-2 . A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m-2 . AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG-CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose-limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m-2 IV every 21 days and approximately 2.75 mg kg-1 PO EOD, respectively. The dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials.

Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours.

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.

Immunophenotypic and histologic classification of 50 cases of feline gastrointestinal lymphoma.

The purpose of this study was to determine the immunophenotype and histologic classification of 50 cases of feline gastrointestinal lymphoma. Classification was determined using the National Cancer Institute Working Formulation and the Revised European and American Lymphoma/World Health Organization classification system. Tissue sections were stained with HE, phosphotungstic acid hematoxylin, anti-CD3, anti-CD79a, and anti-BLA.36. Overall, B-cell tumors predominated at 54% (27/50), including 16 diffuse large with immunoblastic nuclear type, 2 diffuse large with centroblastic nuclear type, 3 small lymphocytic, 4 lymphocytic intermediate type, and 2 T-cell-rich large B-cell lymphomas. T-cell tumors comprised 38% (19/50), including 15 epitheliotropic small lymphocytic and 4 lymphoblastic. Three tumors (6%) were nonreactive for B- and T-cell markers and had eosinophilic cytoplasmic granules when stained with HE. Gastric tumors were diagnosed in 24% (12/50) of cats, and 18% (9/50) were present only in the stomach. All gastric lymphomas were of B-cell lineage. Small intestinal lymphoma predominated, with 74% (37/50) of cats affected: T-cell tumors comprised 52% (19/37); 38% (14/37) were B-cell tumors; 8% (3/37) were nonreactive for B- and T-cell markers; and 2% (1/37) expressed both CD3 and BLA.36. Of the 8 cats (16%) that had lymphoma of the large intestine, 88% (7/8) had B-cell tumors and 12% (1/8) had T-cell tumors. The strongest association between gastrointestinal lymphoma immunophenotype, histologic classification, and location occurred in the stomach, where there was a predominance of diffuse large B-cell lymphoma of immunoblastic nuclear type.

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.

Feline non-ocular melanoma: a retrospective study of 23 cases (1991-1999).

Non-ocular melanoma is considered to be a rare neoplasm in cats; however, more than 150 cases have been reported in the literature since 1961. The objective of this study was to characterise this tumour better by evaluating case outcome and survival data for cats with melanoma and to compare clinical and histopathological findings with those of previous reports. Twenty-three feline non-ocular melanomas were identified, the most common locations being the nose, digit and pinna. Cats with digital melanomas had survival rates similar to their canine counterparts. Histological assignation of benignity, malignancy or junctional activity was not found to be an accurate predictor of clinical behaviour. Melanoma should be considered as a differential diagnosis for cats presenting with pigmented or non-pigmented masses and histopathology is essential for definitive diagnosis, as other tumours may clinically appear quite similar. Regular follow-up examinations are recommended indefinitely for benign or malignant feline melanomas.