The use of low‐dose metronomic chemotherapy in dogs—insight into a modern cancer field

Abstract

The era of chemotherapy, which started in the middle of the last century, has been ruled by the routine use of dose-intense protocols, based on the "maximum-tolerated dose" concept. By promoting a balance between patient's quality of life and the goal of rapidly killing as many tumour cells as possible, these protocols still play a prominent role in veterinary oncology.However, with the opening of a new millennium, metronomic chemotherapy (MC) started to be considered a possible alternative to traditional dose-intense chemotherapy. Characterized by a long-term daily administration of lower doses of cytotoxic drugs, this new modality stands out for its unique combination of effects, namely on neovascularization, immune response and tumour dormancy. This article reviews the rationale for treatment with MC, its mechanism of action and the main studies conducted in veterinary medicine, and discusses the key challenges yet to be solved. K E Y W O R D Schemotherapy, cytotoxic drugs, dogs, dose-intense, metronomic, review

The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma

“…Systemic drug toxicity was frequent but of mild severity in the current study, and mainly related to the gastrointestinal apparatus. The profile of side effects was in keeping with previously published data on metronomic chemotherapy and toceranib …”

“…The metronomic approach in chemotherapy has become relevant for the treatment of various cancers. 22 The rational to use metronomic chemotherapy in the current study was to reduce the incidence of some of the most serious AEs of conventional doses of chemotherapeutics, such as myelosuppression and gastrointestinal toxicity, and to target the endothelial cells of the growing vasculature. It is well known that angiogenesis is a rate-limiting step during tumorigenesis that promotes tumour cell survival and proliferation by ensuring a supply of oxygen and metabolites.…”

“…The profile of side effects was in keeping with previously published data on metronomic chemotherapy and toceranib. 22,34 This study has several limitations, including the small size of the population and lack of randomization. In particular, dogs were not randomized into treatment groups, therefore owners' financial, logistic and social issues are confounding factors that may have influenced the decision to pursue a less aggressive treatment.…”

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma

“…, Gaspar et al . ). A study found that splenectomised dogs with stage II HSA treated with adjuvant doxorubicin had comparable survival times to those treated with splenectomy and a metronomic protocol which consisted of low‐dose cyclophosphamide, etoposide and piroxicam (Lana et al .…”

Adjuvant anthracycline‐based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi‐institutional retrospective study of the Italian Society of Veterinary Oncology

“…The use of drug regimens that have been designed to euthanize as many tumour cells as possible by treating with MTDs of cytotoxic agents have been challenged recently by the use of metronomic chemotherapy (MC) . The term “metronomic” refers to the scheduling, which consists of chronic, equally spaced and generally low doses of single or combined chemotherapeutic drugs without extended drug‐free breaks.…”