Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
Vet Comp Oncol. 2018 Mar;16(1):E16-E22. doi: 10.1111/vco.12327. Epub 2017 Jun 16.
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 . 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 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m , although transient, does not invite to use this dose in canine oncology patients.
Combretastatin A4-磷酸（CA4P）是一种血管破坏剂，在人类癌症治疗中显示出有前景的结果。本研究的目的是研究 CA4P 在健康犬中的安全性和不良事件，作为在癌症犬中应用 CA4P 的前提。纳入了 10 只健康犬。研究了递增剂量的 CA4P 对身体、血液学和生化学参数、收缩压、心电图、超声心动图变量和整体健康状况的影响。测试了 3 种不同的剂量：50、75 和 100mg/m2。在所有 3 种 CA4P 剂量下，给药后数小时内均观察到恶心、腹部不适和腹泻。同样，所有犬均出现轻度中性粒细胞减少症。75 和 100mg/m2 的剂量还会引起呕吐和血清心肌肌钙蛋白 I 水平升高。100mg/m2 时，还观察到轻度高血压和高级别神经毒性。在健康犬中，高达 75mg/m2 的剂量似乎耐受良好。虽然短暂，但在 100mg/m2 时观察到的神经毒性的严重程度不建议在犬肿瘤患者中使用该剂量。
