Radiation therapy of canine brain masses.

This article evaluates the responses of 14 dogs with brain masses using orthovoltage irradiation for definitive treatment. Dogs were anesthetized for computed tomography (CT) examination, formation of head immobilization and positioning devices, radiation treatment simulation, and treatments. Total doses of 39 Gy (9 dogs) or 45 Gy (5 dogs) to the tumor were administered over 25 to 41 days. Two or three portals (parallel opposed lateral with or without a dorsal field) were used. Treatment volumes included the tumor and peritumoral edema, as determined by CT scan, and a 1-cm margin. Histopathologic diagnoses were available in 9 of 14 dogs. There were 4 meningiomas, 1 lymphosarcoma, 1 pituitary adenoma, 1 metastatic anaplastic carcinoma, 1 anaplastic oligodendroglioma and 1 dog with granulomatous meningoencephalitis. At the end of radiation therapy, 10 dogs could be evaluated for progression of clinical signs: 3 dogs deteriorated or failed to improve, and 7 dogs improved. At the time of analysis, all dogs were dead. Mean and median survival times, measured from the beginning of radiation, were 345 and 489 days, respectively. This was compared with mean survival times of 30 to 81 days reported in the literature for dogs with brain tumors that did not receive treatment. The median survival time of 9 dogs treated with 39 Gy was 153 days, versus 519 days for 5 dogs that received 45 Gy. It appears that radiation therapy prolongs survival times for dogs with brain masses. Although megavoltage therapy would be optimal, orthovoltage radiation can be applied in total doses of 45 Gy in 3.75 Gy fractions over 28 days without adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.

Technique, pharmacokinetics, toxicity, and efficacy of intratumoral etanidazole and radiotherapy for treatment of spontaneous feline oral squamous cell carcinoma.

The histologic appearance, locoregional recurrence, and rate/site of metastases of spontaneous feline oral squamous cell carcinoma are similar to head and neck cancer in humans. A feasibility study of intratumoral Etanidazole, a hypoxic cell sensitizer, and radiation therapy were instituted in this model. Eleven cats with feline squamous cell carcinoma were treated with intratumoral Etanidazole and radiation therapy. Total Etanidazole doses were 1.5-24.0 gms/m2 (0.5-6.9 gms). The tumor partial response rate was 100% (11/11); the median volume regression was 70%. All cats have died as a result of tumor recurrence or tumor-related complications. Median survival was 116 days. Ten cats have been autopsied. Non-necrotic and necrotic tumor cells were identified at the treatment site in all cats. Pharmacokinetic studies were performed in six cats. Following intravenous infusion, the plasma elimination of the Etanidazole was biexponential. The systemic availability following intratumoral administration was 61.2 +/- 21.1%. Peak plasma Etanidazole levels were observed 14 minutes following intratumoral injection, after which elimination was biexponential. Thirty minutes following intratumoral Etanidazole administration, tumor Etanidazole levels were 62.8% of plasma levels. Feline squamous cell carcinoma appears to be a useful model of human head and neck cancer. Cats tolerate substantial doses of intratumoral and intravenous Etanidazole. Etanidazole and radiation therapy cause rapid regression, but not cure, of feline squamous cell carcinoma. There is a similarity between the intravenous kinetics of Etanidazole in humans and cats. Further studies in this model are planned.

5-Fluorouracil treatment of a human colon adenocarcinoma implanted in the subrenal capsule site of athymic mice.

5-Fluorouracil was used in the treatment of a recently established. human adenocolon carcinoma implanted in the subrenal capsule site of athymic mice as part of a program to determine the relative effectiveness of antitumor agents in the treatment of human tumors grown as xenografts and in the clinic. 5-Fluorouracil treatments resulted in a dose-dependent inhibition of tumor growth under the two examined schedules (five daily doses and three doses every 4 days) when administered either i.v. or i.p. The various schedules and routes resulted in similar patterns of antitumor effects when the data were based on the endpoints of either final tumor weight, change in tumor weight, or relative tumor weight. Assessments of cell viability based on histological examination of tumored kidneys resulted in a downward displacement of the dose-response curves but did not alter their shape or the interpretation of the data. Although approximately 1-mm3 tumor fragments were implanted, variability of size was allowed. Tumor growth was not dependent on the initial size of the implant, as shown by a comparison between the initial individual or average tumor sizes and the final individual or average tumor sizes, respectively. The antitumor effects of the 5-fluorouracil could have been determined on the basis of final tumor weight alone. The inhibition of tumor growth was accompanied by weight loss in treated mice as compared with controls. At lower doses, however, the weight loss of the mice was not extensive, which indicated that the inhibition of tumor growth was, at least in part, attributable to some selective antitumor action of the 5-FUra. The greatest inhibition of tumor growth, however, was accompanied by the most extensive animal weight loss. This correlation raised the question of the degree to which the tumor growth inhibition observed was a consequence of nonspecific drug toxicity to the host. The current results stress the importance of detailed investigations into the nature of host-tumor parameters in order to assess the antitumor activity of candidate drugs in the treatment of human tumor xenografts.