Treatment of Canine Oral Melanoma with Adjuvant Chemotherapy and Immunotherapy

Gleidice Eunice Lavalle, Carla Emanuela Tertuliano Caires, Stéfane Valgas Teixeira, Rúbia Monteiro de Castro Cunha, Rubens Antônio Carneiro


Background: Melanoma is the most frequent cancer in the canine oral cavity. It shows an aggressive behavior, characterized by rapid and invasive growth and high metastatic potential. Metastasis is seen in more than 80% of dogs at time of death. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poor prognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to the disease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanoma and treated with adjuvant chemotherapy and immunotherapy.

Materials, Methods & Results:A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocytic melanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oral malignant melanoma. Tumor size (T1: < 2 cm; T2: 2 - 4 cm; T3: > 4 cm), regional metastasis (N0: no metastasis; N1: metastasis) and presence of distant metastasis (M0: no metastasis; M1: metastasis) are evaluated. Then, cases were divided into 4 stages: I (T1 N0 M0), II (T2 N0 M0), III (T3 N0-1 M0, Tx N1 M0) and IV (Tx Nx M1). Diagnoses were confirmed with histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were divided into 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted to surgery associated with adjuvant chemotherapy with four 21-day cycles of carboplatin (300 mg/m2) and immunotherapy with six 7-day cycles of interferon-α (3 x 106 IU/m2) were included in group 2 (G2). Twenty dogs diagnosed with oral melanoma were evaluated: 3 were included in G1 and 17 in G2. Considering clinical staging of the dogs: 7 stage II, 12 stage III and only 1 stage IV. There was no stage I patients. In poorly differentiated neoplasias, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Patient follow-up was obtained through the evaluation of patient records and telephone interviews with owners. The overall survival time (OS) was defined by the period (in days) between the date of surgical excision and the death caused by the disease. Median overall survival time was 86 days for animals in G1 and 894 days for animals in G2 (P = 0.01).

Discussion: Carboplatin was considered an appropriate cytostatic drug to treat microscopic disease in oral melanoma. INF-α was chosen for immunotherapy in this study because it promotes immune system stimulation associated with an indirect antiproliferative effect on neoplastic cells. The association of INF-α and carboplatin resulted in a significant increase in overall survival, when compared to the literature, suggesting that association of chemotherapy and immunomodulation is an important strategy in the treatment of canine oral melanoma. Controlled prospective randomized trials are necessary to confirm the benefits of chemotherapy and immunotherapy association to treat canine oral melanoma. Adjuvant therapy with chemotherapy and immunotherapy was considered effective to increase overall survival and maintained quality of life of dogs diagnosed with oral melanoma.

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