For many years, research on anticancer therapy has focussed almost exclusively on targeting cancer cells directly, to selectively kill them or restrict their growth. But limited advances in this strategy have led researchers to shift their attention to other potential targets. Active research is now on-going on targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising class of anticancer drugs that are currently under investigation as a sole or combined therapy in human cancer patients. This article will briefly touch on the history and biology of combretastatin A4-phosphate (CA4P) as a typical example of VDAs and will concentrate on the side effects that can be expected when used in veterinary patients. Particularly, the pathogenesis of these side effects and how they may be prevented and/or treated will be discussed. The purpose of this article is to illustrate the potentials of CA4P as anticancer therapy in veterinary oncology patients.

Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12).

Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer.Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m −2 .At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m −2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m −2 , low-grade hypertension and high-grade neurotoxicity were also observed.In healthy dogs, doses up to 75 mg m −2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m −2 , although transient, does not invite to use this dose in canine oncology patients. K E Y W O R D Santicancer therapy, combretastatin A4-phosphate, dogs, dose-escalation, vascular disrupting agent

One of the major challenges in surgical oncology is the intraoperative discrimination of tumoural versus healthy tissue. Until today, surgeons rely on visual inspection and palpation to define the tumoural margins during surgery and, unfortunately, for various cancer types, the local recurrence rate thus remains unacceptably high. Near-infrared (NIR) fluorescence imaging is an optical imaging technique that can provide real-time preoperative and intraoperative information after administration of a fluorescent probe that emits NIR light once exposed to a NIR light source. This technique is safe, cost-effective and technically easy. Several NIR fluorescent probes are currently studied for their ability to highlight neoplastic cells. In addition, NIR fluorescence imaging holds great promise for sentinel lymph node mapping. The aim of this manuscript is to provide a literature review of the current organic NIR fluorescent probes tested in the light of human oncology and to introduce fluorescence imaging as a valuable asset in veterinary oncology.