A prospective, multi-centre, Veterinary Radiation Therapy Oncology Group study reveals potential efficacy of toceranib phosphate (Palladia) as a primary or adjuvant agent in the treatment of canine nasal carcinoma.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.

Evaluation of a novel immunomodulator composed of human chorionic gonadotropin and bacillus Calmette-Guerin for treatment of canine mast cell tumors in clinically affected dogs.

OBJECTIVE: To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine. ANIMALS: 95 dogs with measurable grade II or III mast cell tumors. PROCEDURES: Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m(2), IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed. RESULTS: 46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (>or=50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group. CONCLUSIONS AND CLINICAL RELEVANCE: hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.

Unexpected toxicity following use of gemcitabine as a radiosensitizer in head and neck carcinomas: a veterinary radiation therapy oncology group pilot study.

Gemcitabine (2',2'-difluorodeoxycytidine) was given intravenously twice weekly to 10 cats with oral squamous cell carcinoma and 15 dogs with nasal carcinoma undergoing radiotherapy as a radiosensitizing agent. The average total radiation dose was 50 Gy for dogs and 54 Gy for cats given Monday-Friday (planned dose of 54 and 57 Gy, respectively). Dogs received an average of five doses of gemcitabine beginning at 50 mg/m2, and cats received an average of five doses of gemcitabine beginning at 25 mg/m2. Twelve of 15 dogs and five of 10 cats required chemotherapy dose reduction or postponement because of hematologic or normal tissue toxicity. The results herein do not support the use of gemcitabine at the studied dose and schedule, as significant hematologic and local tissue toxicity was observed in the studied patients. Pharmacokinetic data are necessary to best define the efficacy and optimal dose and schedule of gemcitabine in combination with traditional radiotherapy.