Paper Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case – control prospective study C. Arenas, L. Peña, J. L. Granados-Soler, M. D. Pérez-Alenza Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. Introduction Canine mammary tumours (CMTs) are the most common neo- plasms in female dogs. Approximately 50 per cent of CMTs are malignant, many of which metastasise (Perez Alenza and others 2000). Cyclooxygenase (Cox) enzymes catalyse prostaglandin for- mation from arachidonic acid. There are two Cox isoforms. Cyclooxygenase-1 (Cox-1) is constitutively expressed in many tissues, while cyclooxygenase-2 (Cox-2) is inducible by growth factors, inflammatory stimuli and several oncogenes (Fosslien 2000; Yoshimura and others 2003). Cox-2 participates in differ- ent steps of the carcinogenetic process, including stimulation of tumour angiogenesis, decreases tumour apoptosis, increases inva- sion and metastasis and tumour-associated inflammation (Hayes 2007; Tsujii and others 1998). Angiogenesis, the recruitment of new blood vessels, plays a crucial role in tumour growth, and it is an essential component of the metastatic pathway, as it enhances entry of tumour cells into the circulation (Hanahan and Folkman 1996; Zetter 1998). A number of studies have demonstrated that the vascular density of a tumour is correlated with metastasis (Zetter 1998) and some studies have shown that treating experimental animals with primary tumours with angiogenesis inhibitors decreases the formation of metastatic colonies (Taylor and Folkman 1982). Several immunohistochemical studies have shown that Cox-1 and Cox-2 are expressed in CMTs and also that a high expression of Cox-2 is associated with malignancy, it is related to a poor prognosis and it is also associated with tumour angio- genesis in CMTs (Dore and others 2003; Queiroga and others 2007). These findings suggest that Cox-2 inhibitors might be useful in the treatment of malignant CMTs. There are also some studies which have evaluated the efficacy of several postsurgical adjuvant chemotherapy protocols in the treatment of malignant CMTs (Karayannopoulou and others 2001; Simon and others 2006; Tran and others 2014). One study carried out by Lavalle and others (2012) found that several adjuvant proto- cols (including chemotherapy alone or in combination with NSAIDs) for advanced CMTs led to a statistically significant longer overall survival (OS) when compared with surgical treatment alone. The aims of this study were to evaluate the efficacy (disease- free survival (DFS) and OS) and toxicity of a Cox-2 inhibitor ( fir- ocoxib) as adjuvant therapy after surgery for highly malignant (HM)-CMTs and compare it with that of dogs treated with surgery alone or with surgery and chemotherapy. Materials and methods Animals Dogs diagnosed with HM-CMTs at the Veterinary Teaching Hospital (University Complutense, Madrid) (VTH-UCM) were Veterinary Record (2016) doi: 10.1136/vr.103398 C. Arenas, PhD DVM, Department of Veterinary Medicine, University of Cambridge, The Queen’s Veterinary School Hospital, Cambridge, UK L. Peña, PhD, Dipl ECVP , DVM, J. L. Granados-Soler, DVM, M. D. Pérez-Alenza, PhD, DVM, Department of Veterinary Medicine and Science, University Complutense of Madrid, Veterinary School Hospital, Madrid, Spain E-mail for correspondence: caroarenas10@hotmail.com Provenance: Not commissioned; internally peer reviewed Accepted June 14, 2016 July 30, 2016 | Veterinary Record Paper group.bmj.com on July 29, 2016 - Published by http://veterinaryrecord.bmj.com/ Downloaded from