Metronomic chemotherapy: bridging theory to clinical application in canine and feline oncology.

Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic success. Traditionally, chemotherapy protocols are based on classic cytostatic drugs under the concept of maximum tolerated dose (MTD), which has been associated with a greater risk of toxicity and resistance. Thus, new therapeutic alternatives have emerged, such as metronomic chemotherapy (MC), introducing a new paradigm in cancer treatment. MC consists of administering low doses of chemotherapy drugs continuously over a long period of time, modulating the tumour microenvironment (TME) due to the combination of cytotoxic, antiangiogenic and immunomodulatory effects. This multi-targeted therapy has been described as a treatment option in several canine and feline cancers since 2007, with positive results already published in the literature, particularly in mammary carcinomas and soft tissue sarcomas in dogs. The aim of this review article is to describe the current knowledge about the use of MC in small animal oncology, with emphasis on its mechanisms of action, the most commonly used drugs and clinical outcome.

Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features.

Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.

Anaesthesia in Veterinary Oncology: The Effects of Surgery, Volatile and Intravenous Anaesthetics on the Immune System and Tumour Spread.

Throughout the course of oncological disease, the majority of patients require surgical, anaesthetic and analgesic intervention. However, during the perioperative period, anaesthetic agents and techniques, surgical tissue trauma, adjuvant drugs for local pain and inflammation and other non-pharmacological factors, such as blood transfusions, hydration, temperature and nutrition, may influence the prognosis of the disease. These factors significantly impact the oncologic patient's immune response, which is the primary barrier to tumour progress, promoting a window of vulnerability for its dissemination and recurrence. More research is required to ascertain which anaesthetics and techniques have immunoprotective and anti-tumour effects, which will contribute to developing novel anaesthetic strategies in veterinary medicine.

Neutrophil-to-lymphocyte ratio is an independent prognostic marker for feline mammary carcinomas.

Blood leukocyte counts and respective derived ratios have been described as potential prognostic markers in several tumours in veterinary oncology. This study aimed to evaluate peripheral blood leukocyte subpopulations and neutrophil-to-lymphocyte ratio (NLR) as prognostic factors for feline mammary carcinomas (FMC). Medical records from cats diagnosed with FMC between 2017 to 2019 were reviewed. Cats were included if fully staged, classified as WHO stage I to III, and submitted to mastectomy. Cats were excluded if they had evidence of other diseases. Forty-nine cats were included. The study endpoints were disease-free interval (DFI) and tumour-specific survival (TSS). The median DFI and TSS were 389 days and 528 days respectively. In the univariate analysis, higher values of total white blood cell count (WBC), neutrophil count (NEU) and NLR were identified as significant prognostic factors for both endpoints (P < .05). On the multivariate analysis, NLR remained an independent prognostic factor for TSS (P = .024). In the receiver operating characteristic curve analysis, the estimated cut-off for WBC was 8.49 × 109 /L (DFI and TSS); for NEU was 4.62 × 109 /L (DFI) and 6.65 × 109 /L (TSS) and for NLR was 2.46. These cut-offs were significant prognostic factors for DFI and TSS (P < .05). NLR cut-off remained an independent prognostic factor for both DFI (P = .032) and TSS (P = .043) in the multivariable analysis. Our results suggest that NLR, NEU, and WBC can be important non-invasive presurgical prognostic markers, and that NLR is an independent prognostic marker for FMC. Prospective studies are warranted to validate its clinical use.

Adjuvant doxorubicin vs metronomic cyclophosphamide and meloxicam vs surgery alone for cats with mammary carcinomas: A retrospective study of 137 cases.

This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.