Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary leaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable disiroxicam (Feldene) is a nonsteroidal anti-inflammatory P drug primarily used to treat arthritis in humans.' It has also been reported to have antitumor activity in chemically inducal2-' and transplanted* tumors in rodents and in metastatic tumors in people.' We previously reported a phase I clinical trial of piroxicam in 62 dogs with naturally occurring tumors and identified dose-related gastrointestinal toxicity and subclinical renal toxicity.'o Antitumor activity was observed in this phase 1 trial in dogs with transitional cell carcinoma (TCC) of the urinary bladder." To hrther investigate the antitumor activity of piroxicam, we conducted a phase I1 clinical trial in 25 dogs with TCC of the bladder. The study reported here includes 9 dogs from the phase I trial and 25 dogs from the phase I1 trial. Although the purpose of a phase I trial is to evaluate drug doses and toxicity, useful information on tumor response and survival was available in the dogs with TCC in the phase I trial we conducted." Therefore, these dogs were included in this report. Materials and Methods Clinical Trial DesignEntry requirements for this study included the presence of measurable (by cystography), histopathologically confirmed TCC of the urinary bladder, performance status consistent with expected minimum survival of6 weeks, and informed consent by the owner. Dogs that had previously received chemotherapy had evidence of tumor progression on that therapy, and a minimum of 3 weeks was required between the last chemotherapy and entry into this trial.Dogs were evaluated at the Purdue University Veterinary Teaching Hospital on days 0, 28, and 56. These evaluations included physical examination, complete blood count, serum biochemistry profile, urinalysis, thoracic radiography, and cystography (pneumocystography or double contrast cystography). Care was taken to perform the cystography in the same manner (same radiographic technique, same amount of contrast material) for each evaluation of a patient. Piroxicam was administered orally at a dose of 0.3 mg/kg sid. This dose was established based on a previous phase I clinical trial." When secondary bacteria...

Reports of prognosis based on clinical staging of canine oral malignant melanoma consistently differ. To determine the prognostic utility of the World Health Organization (WHO) tumour, node, metastasis (TNM) system and a proposed alternative staging system, a retrospective study of 41 dogs with naturally occurring oral malignant melanoma was conducted. All the tumours were clinically staged, removed surgically and the tissues histologically reviewed. Treatment responses were correlated with the clinical and histological features reported to have prognostic utility. Dogs presenting with a tumour smaller than 8 cm3, located on the rostral mandible or caudal maxilla, and, or, having a tumour mitotic index of 3 or less had a significantly longer remission length and survival time than did other dogs, regardless of the treatment selected. Treatment by radical surgical excision (eg, hemimandibulectomy) resulted in longer remission lengths and survival times than any other type of treatment regardless of whether or not surgical margins were determined to be free of residual tumour. The WHO system failed to identify a prognostic difference between dogs of a differing clinical stage. An alternative system derived from significant features mentioned above did identify a prognostic difference and is recommended for further evaluation regarding its utility in the pre‐treatment evaluation and clinical staging of other dogs with oral ‐malignant melanoma.

A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the histology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation.

Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastrointestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.

Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.