Evaluation of Cimetidine as a Therapy for Dermal Melanomatosis in Grey Horse

This paper describes a clinically controlled study on the effectiveness of cimetidine an h2 receptor antagonist for the treatment of melanoma in grey horses. Fifteen grey horses (age range 18 to 27 years) with dermal melanomatosis were divided in three groups. group A served as the control group; groups B and C received cimetidine at two different protocols for 60 days (3.5 mg/kg PO, BID and 7.5 mg/kg PO, SID). The number and size of the masses was monitored before, during and after therapy. No differences were found between groups regarding number and size of melanomas before and after treatments (p >0.05). Only in one horse it was possible to notice a slight size reduction of some of the masses however this may have been due to the anti-inflammatory effect of cimetidine as already demonstrated previously. It was concluded that cimetidine is not effective in treating dermal melanomatosis of grey horses. Differences of effectiveness in other studies could possibly be due to the variants of melanomas treated or to different treatment protocols. Further controlled studies are necessary to evaluate cimetidine effectiveness on different type of melanomas and other neoplasias arising from tissues other than skin. Also the mechanism of action of cimetidine on horse melanoma requires further investigation. INTRODUCTION Melanoma is one of the most common cutaneous tumors of the horse and represents 3.8% of the total equine neoplasias [1]. Such neoplasia affects mainly grey horses older than 6 years of age even though it can be found in horses of any coat color where it usually tends to be more aggressive [2, 3]. According to some authors, 80% of grey horses older than 15 years are likely to be affected by multiple melanomas (melanomatosis) [4, 5, 6]. The most common localizations of the tumor are the perineal and/or perianal region, the external genitalia, the ventral surface of the tail and parotid region, but it is possible to find it in many other sites like eyelids, coronary band, vertebral region, nasal cavity and theoretically in any other regions of the body [7, 8]. Although it represents a very common equine tumour, the exact nature of the grey horse melanoma is not completely understood. Some authors define it as a true malignancy [9] while other suggest that it may be a storage disorder associated with the depigmentation process that occurs in grey horses [6, 8, 10]. The graying of hair in horses represents a risk factor and it seems to be the result of a genetic mutation not detected in humans [11]. Valentine described four distinct syndromes [2]: melanocytic naevus (affecting mainly young horses), dermal melanoma (1 or 2 masses affecting mostly mature grey horses), dermal melanomatosis (affecting aged grey horse) and anaplastic malignant melanoma (reported in non-grey horse and with histological features of malignancy). Melanoma of grey horses presents usually as a benign tumor, probably due to the existence of unknown factors that prevent or delay the spread of the tumor [3, 12]. Metastatic spread of melanoma is possible to almost all organs of the body and is common in aged grey horses often without related symptoms [13, 14]. Benign melanoma of grey horses seem to share some features with human blue naevus which only occasionally undergoes malignant transformation [3, 12] and with animaltype melanoma, a recently reported rare variant of melanoma in humans, the name of which is derived from its histological appearance which is similar to that described in melanomas occurring in white or grey horses [15]. Cimetidine has been demonstrated to have anti-cancer effects on colorectal cancer, melanoma, renal cell carcinoma and salivary gland cancer in human [16, 17]. It seem to have an immunomodulatory effect [18] resulting in an increase