How I Treat Oral Melanoma Malignum

Learning Objective

Presentation of surgical and adjuvant therapy of oral melanoma in dogs and cats. Sharing own experiences and brief update on available treatment options.

Introduction

Oral Melanoma is the most frequently diagnosed malignant tumor in the oral cavity in dogs and the second most frequent one in cats. Management of this condition may be very frustrating because of its specific biology that causes failure of many surgical procedures. It is relatively common that the oral MM is diagnosed at the stage of growth that allows only for palliative surgery. There are numerous studies that evaluate different supporting treatment which follows the oral surgery. The further treatment includes radiation therapy, immunotherapy with use of melanoma vaccine and cytotoxic therapy. Many papers and experiences show possible efficiency of immune-related drugs and the procedures that involve immune system of the patient.

Resective treatment remains major treatment modality of MM oral tumors in all patients without metastases. In most cases surgery is radical and the margin sections are wide if surgery is possible.

Surgical excision of very small and early lesions may occasionally be successful, but for larger lesions surgery is no more than palliative, leading to a better quality of life for the patient. Metastasis to the regional lymph nodes and lungs takes place at an early stage in the majority of the patients. Median survival time with aggressive surgery with or without irradiation is 5–9 months, and less than 25% of the patients survive longer than a year. There is no optimal protocol available for control or prevention of distant metastasis. Recently a vaccine became available, which doubled survival times in a clinical trial. Other possible future treatments may target vascular endothelial growth factor (antiangiogenic therapy). Recently it has been reported that oral MM cells in dogs show over-expression of COX-2, suggesting that COX-2 inhibitors may be useful in the treatment of canine oral MM.

This author designs treatment plans based on medical records of the patient and dedication of the pet owner. If the tumor is resectable - it is the first treatment episode. Surgery does not have radical extent with margin sections 3 cm and resection of ipsilateral mandibular and retropharyngeal lymph nodes.

Depending on recovery and general condition of the patient the next step is cytotoxic therapy performed 12–14 days after surgery. Cytotoxic protocol is based on Dacarbazine (200 mg/m2) and Carboplatin (300 mg/m2). Further treatment always includes adjuvant treatment with Interferon-alpha (or omega in cats) supplements acting stimulative for immune system. For those patients who may afford radiation therapy it is advised, but this has to be performed abroad due to lack of radiation therapy center in the area. Radiation therapy can be thought of as an intense x-ray beam that is delivered to the scar or tumor only. It can be used in two different settings; postoperatively or if a tumor is too large to remove. Oral melanomas tend to be very responsive to radiation therapy whether there is just a scar or a tumor still present. The radiation therapy protocol for oral melanoma is a treatment twice weekly for seven total treatments. The mouth can be very sensitive to radiation therapy and side effects can include redness, inflammation, and ulceration of the treatment site, as well as an increase in salivation that rarely affects appetite or energy level.

Every patient is also recommended to consider use of melanoma vaccine (Oncept, Merial).

The melanoma vaccine contains the human DNA sequence encoding a specific protein only found within melanocytes called tyrosinase. Tyrosinase is an enzyme crucial to the melanocyte’s ability to produce melanin (pigment), and also to the survival of the melanocyte itself. Once injected into the dog, the human DNA segment is processed so the dog’s body actually generates small amounts of the human tyrosinase protein. Just like the weakened disease-causing organism in a conventional vaccination, the human tyrosinase protein is recognized by the dog’s immune system as foreign. Subsequently, the dog’s immune system will generate a response towards the human tyrosinase protein designed to destroy it.

Survival time differs and is linked to stage of tumor, its histopathologic type, and location. The average survival time of untreated dogs is reported to be 65 days. Average survival times and 1-year survival rates of dogs treated with surgery alone range from 5–17 months and 21–27%, respectively. In general, the smaller the tumor and the closer to the front of the mouth that it is, the better the prognosis.