Adjuvant chemotherapy with mitoxantrone for cats with mammary carcinomas treated with radical mastectomy.

OBJECTIVES: The purpose of this study was to investigate the disease-free interval, survival time and adverse events of a combined treatment approach in cats with mammary malignant tumors using radical mastectomy and adjuvant mitoxantrone. METHODS: All cats underwent surgery to remove the mammary chain containing the tumors. A 3 cm margin was obtained around removed tumors. For staging purposes, regional inguinal lymphadenectomy was performed in all cases. After histopathology, cats were staged according to the World Health Organization's (WHO) staging system. Chemotherapy with mitoxantrone was started 15-30 days after surgery (6 mg/m(2) IV every 21 days for four cycles) with the objective of delaying metastasis. RESULTS: Three cats were intact, one cat was early spayed, four cats were late spayed and four cats were spayed at an unknown age. Based on the WHO's staging system, six cats were classified as stage I and six cats as stage III. The median disease-free interval and survival time were 360 and 480 days, respectively. Four (33%) cats received four doses of mitoxantrone, four (33%) cats received three doses and four (33%) cats received only one dose. The most frequent adverse effects of chemotherapy were azotemia, anorexia, leukopenia and vomiting. CONCLUSIONS AND RELEVANCE: Adjuvant mitoxantrone chemotherapy may be an option for feline mammary tumors. Further, sufficiently powered, randomized prospective trials are necessary to determine if mitoxantrone is superior, inferior or equivalent to doxorubicin in the adjuvant setting.

Radiation therapy for feline cutaneous squamous cell carcinoma using a hypofractionated protocol.

The objective of this paper was to evaluate the efficacy of a hypofractionated radiation protocol for feline facial squamous cell carcinoma (SCC). Twenty-five histologically confirmed SCCs in 15 cats were treated with four fractions of 7.6-10Gy each, with 1 week intervals. The equipment used was a linear accelerator Clinac 2100 delivering electron beam of 4 or 6MeV, and a bolus of 5 or 10mm was used in all lesions. Of the lesions, 44% were staged as T4, 16% as T3, 8% as T2 and 32% as T1. Of the irradiated lesions, 40% had complete response, 12% had partial response and 48% had no response (NR) to the treatment. For T1 tumors, 62.5% had complete remission. Mean overall survival time was 224 days. Owners requested euthanasia of cats having NR to the treatment. Mean disease free time was 271 days. Side effects observed were skin erythema, epilation, ulceration and conjunctivitis, which were graded according to Veterinary Radiation Therapy Oncology Group (VRTOG) toxicity criteria. Response rates found in this study (52%) were lower when compared to other protocols, probably due to technique differences, such as fractionation schedule, bolus thickness and energy penetration depth. However, the hypofractionated radiation protocol was considered safe for feline facial SCC. Modifications of this protocol are being planned with the objective of improving the cure rates in the future.

Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines.

Recently, Boron neutron capture therapy (BNCT) was successfully applied to treat experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa, with no damage to normal tissue. It was also shown that treating spontaneous nasal planum SCC in terminal feline patients with low dose BNCT is safe and feasible. In an extension of this work, the present study aimed at evaluation of the response of tumor and dose-limiting normal tissues to potentially therapeutic BNCT doses. Biodistribution studies with (10)B-boronophenylalanine (BPA enriched in (10)B) as a (10)B carrier were performed on three felines that showed advanced nasal planum SCC without any standard therapeutic option. Following the biodistribution studies, BNCT mediated by (10)BPA was done using the thermalized epithermal neutron beam at the RA-6 Nuclear Reactor. Follow-up included clinical evaluation, assessment of macroscopic tumor and normal tissue response and biopsies for histopathological analysis. The treated animals did not show any apparent radiation-induced toxicity. All three animals exhibited partial tumor control and an improvement in clinical condition. Enhanced therapeutic efficacy was associated with a high (10)B content of the tumor and a small tumor size. BNCT is therefore believed to be potentially effective in the treatment of spontaneous SCC. However, improvement in targeting (10)B into all tumor cells and delivering a sufficient dose at a greater depth are still required for the treatment of deep-seated, large tumors. Future studies are needed to evaluate the potential efficacy of the dual mode cellular (e.g. BPA-BNCT) and vascular (e.g. GB-10-BNCT) targeting protocol in a preclinical scenario, employing combinations of (10)B compounds with different properties and complementary uptake mechanisms.

BNCT of 3 cases of spontaneous head and neck cancer in feline patients.

Having demonstrated BPA-BNCT induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of the RA-1 Reactor within a preclinical context. The biodistribution studies showed that, in all three cases evaluated, BPA delivered absolute boron values to tumor in the range that proved therapeutically useful in the experimental model of SCC. BPA-BNCT studies showed no radiotoxic effects, partial tumor control in terms of impaired growth and partial necrosis, an improvement in clinical condition and prolonged survival beyond the terminal condition of the feline patients at the time of recruitment.