Dudley L. McCaw

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.

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–2was 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.

Proteomics of Canine Lymphoma Identifies Potential Cancer-Specific Protein Markers

Purpose: Early diagnosis of cancer is crucial for the success of treatment of the disease, and there is a need for markers whose differential expression between disease and normal tissue could be used as a diagnostic tool. Spontaneously occurring malignancies in pets provide a logical tool for translational research for human oncology. Lymphoma, one of the most common neoplasms in dogs, is similar to human non–Hodgkins lymphoma and could serve as an experimental model system. Experimental Design: Thirteen lymph nodes from normal dogs and 11 lymph nodes from dogs with B-cell lymphoma were subjected to proteomic analysis using two-dimensional PAGE separation and matrix-assisted laser desorption/ionization time-of-flight analysis. Results: A total of 93 differentially expressed spots was subjected to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry analysis, and several proteins that showed differential expression were identified. Of these, prolidase (proline dipeptidase), triosephosphate isomerase, and glutathione S-transferase were down-regulated in lymphoma samples, whereas macrophage capping protein was up-regulated in the lymphoma samples. Conclusions: These proteins represent potential markers for the diagnosis of lymphoma and should be further investigated in human samples for validation of their utility as diagnostic markers.

Attempted Photodynamic Therapy of Squamous Cell Carcinoma in the Casque of a Great Hornbill (Buceros bicornis)

Abstract A 33-year-old male great hornbill (Buceros bicornis) presented with a roughened fissured rostral casque. Physical examination revealed a softened rostral casque and diagnostic tests indicated a squamous cell carcinoma. A course of photodynamic therapy was begun in which cytotoxic oxygen radicals were generated to destroy tumor cells. Two courses of photodynamic therapy reduced the size and spread of the tumor initially but failed to eliminate the cancer. Upon physical deterioration and progression of the neoplasia, the bird was euthanized.

RADIATION AND CISPLATIN FOR TREATMENT OF CANINE URINARY BLADDER CARCINOMA

Two cases of canine urinary bladder carcinoma were treated with combined radiation and cisplatin. Total radiation dose was 4400 cGy for one dog and 4800 cCy for the other. Cobalt 60 radiation was fractioned using 400 cGy per fraction. Cisplatin was administered intraarterially at a dose of 50 mg/m2 divided equally six to seven hours before the first three radiation fractions. Cisplatin was administered before the last three radiation fractions at the same dose and time, but was infused intravenously. Objective evaluation using double contrast cystograms revealed reduction in tumor size in both dogs. The therapy was well-tolerated with minimal side effects.

Pharmacokinetics of pyropheophorbide‐a‐hexyl ether in the dog

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.

Attempted photodynamic therapy against patagial squamous cell carcinoma in an African rose-ringed parakeet (Psittacula krameri).

Abstract A 5-yr-old female African rose-ringed parakeet (Psittacula krameri) presented with an ulcerated mass in the medial postpatagial area of the right wing. Biopsy specimens of the mass demonstrated a well-differentiated squamous cell carcinoma. Photodynamic therapy resulted in tumor cell necrosis and initial reduction in tumor burden, but complete remission was not achieved. Based on this and other avian cases, it appears that photodynamic therapy designed to eradicate squamous cell carcinoma in avian species using protocols modeled after canine, feline, and human photodynamic therapy protocols may not be useful. It is hypothesized that differences in light penetration, photosensitizing agent pharmacokinetics, and wound healing properties in avian species necessitate alteration of photodynamic therapy protocols if this treatment modality is to be effective in avian oncology.

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.

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.

Intermittent Single-Agent Doxorubicin for the Treatment of Canine B-Cell Lymphoma

Canine B-cell lymphoma is a highly treatable disease, but cost and logistical factors may hamper an owners ability to pursue treatment of their pet with this disease. The authors evaluated the use of single-agent doxorubicin in an intermittent fashion for efficacy in the treatment of this disease. Morphologic and clinical data were analyzed for prognostic significance. Eighteen dogs with B-cell lymphoma, all with multicentric disease, were enrolled. The overall complete response (CR) rate was 78%, median total doxorubicin remission time (TDR) was 80.5 days, and median overall survival (OS) was 169.5 days. The median number of doxorubicin doses administered was 4.5. First remission times were significantly affected by clinical stage and substage of disease. Outcome for the dogs in this study were similar to those previously reported for single-agent doxorubicin treatment. Additionally, the intermittent nature of the treatments made the described protocol more feasible for the owners who enrolled their pets in this study. Intermittent single-agent doxorubicin is not a substitute for multiagent chemotherapy protocols in the treatment of canine lymphoma; however, it is a reasonable alternative if the cost and time commitments are limiting factors for an owner.