Melanoma Update

Melanoma is a cancer of the pigmented cells, but not all melanomas contain pigment (termed amelanotic melanoma). Unlike the human counterpart, melanomas in veterinary patients are unlikely UV-radiation induced. In fact, patients with dark coats represent a large proportion of veterinary patients with melanoma. While an etiologic factor has not been found, trauma is suspected as a predisposing factor given that melanocytes divide when the skin is injured.

Cutaneous melanomas typically behave less aggressively than the mucocutaneous and digital forms. Oral melanomas are the most common oral tumors in dogs with Scottish Terriers, golden retrievers, poodles and dachshunds at greater risk. Ocular melanomas, while rare, behave in a distinct fashion whereas other forms of melanoma can have quite variable biological behavior. Special stains (namely, Ki-67) to evaluate the proliferation capabilities of a tumor can provide more reliable information regarding biological behavior, particularly for cutaneous and oral melanomas. Regardless of location, treatment recommendations are the same and consist of aggressive local therapy combined with systemic therapy.

Local treatment entails either surgery or radiation therapy. If good margins can be obtained, wide surgical excision is recommended. Removal of the draining lymph node, if possible, is recommended as up to 40% of “normal” lymph nodes revealed metastatic disease in one study1. Radiation therapy can be used as first line therapy for melanoma with relatively good response (82-94% overall response rate in one study2) or as adjuvant therapy to follow surgery, the latter being important if narrow or dirty margins were obtained. If the draining lymph node was not removed at surgery, current radiation protocols recommend including the local lymph nodes for the best response. Typically, radiation protocols for melanoma consist of six treatments given once a week, though higher doses can be given to reduce the number of treatments for patients considered at risk for anesthesia. Radiation side effects are rare and typically mild in our patients. A sunburn like effect may develop in the irradiated site and the fur may grow back dilute in color (e.g. white).

melanomaSystemic therapy for melanoma consists of either the USDA approved Merial melanoma vaccine (Oncept®) or metronomic chemotherapy. Traditional injectable chemotherapy has been, on the whole, rather unrewarding with responses <30% and short in duration. As such, it is recommended unless used prior to radiation as a radiation sensitizer or in cases where other options have failed. The melanoma vaccine is currently used in canine and equine melanoma since these species have a greater incidence of melanoma. While there are no studies to confirm activity in cats, the vaccine should work in theory as it does in dogs. The vaccine uses human DNA that stimulates the patient’s immune system to recognize the melanoma as foreign and, so, try to eradicate it. The prospective study evaluating the melanoma vaccine demonstrated a significant improvement in survival vs. surgery alone. Even in patients with advanced disease responses have been noted and traditionally whereby the average survival with pulmonary metastatic was 6 weeks, nearly 20% of patients were still alive at one year.

Alternatively, metronomic chemotherapy entails daily administration of low doses of chemotherapy with an agent called cyclophosphamide. This protocol aims at inhibiting new blood vessel formation, thereby depriving cancer cells of essential oxygen and nutrients needed to grow and spread, ultimately slowing progression of disease. Interestingly, metronomic therapy may also stimulate the immune system, thus could aid in efficacy with the melanoma vaccine. Side effects with metronomic therapy are uncommon but urinary bladder inflammation thus consistent evaluation of the urine is needed while on therapy.

Given the relatively high metastatic potential of melanomas in general, many patients that do not pursue treatment – either local or systemic – succumb to metastatic disease within 3 months. With aggressive local treatment and some form of systemic therapy, survival times can be extended from 6 to 12 months, depending on the modality (or modalities) chosen. Choosing to treat melanoma in our patients can double to quadruple median survival times and quality of life during that time is good to excellent.

Submitted by Dr. Daniel Meritet
The Veterinary Cancer Center

References:
1. Withrow, S et al. Small Animal Clinical Oncology. 5th Ed. Elsevier: St. Louis. pp 321 – 334. 2013
2. Williams, LE et al: Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001), Journal of American Veterinary Medical Association. 222(9): 1234-1236. 2003.
3. Proulx, DR et al: A retrospective analysis of 140 dogs with oral melanomas treated with external beam irradiation, Veterinary Radiology and Ultrasound. 44 (3):352- 359. 2003.

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