Receptor tyrosine kinase inhibitors (TKIs) are used to treat human and canine cancers and may be combined with radiation therapy (RT) to enhance tumor control due their anticancer and antiangiogenic effects; however, recent case reports have emerged describing incidences of gastrointestinal toxicity when antiangiogenic therapies are combined with hypofractionated radiotherapy in human cancer patients. We evaluated the incidence of gastrointestinal (GI) toxicity in dogs receiving concurrent hypofractionated abdominal RT and the TKI toceranib (TOC) compared to those receiving abdominal RT alone, TOC alone, or concurrent non-abdominal RT and TOC. Medical records of canine cancer patients were retrospectively reviewed and identified dogs were included in the following treatment categories: dogs which received RT to a portion of the abdomen and concurrent TOC (n = 19), abdominal RT alone (n-29), TOC alone (n = 20), or non-abdominal RT plus TOC (n = 9). Toxicities were graded using the Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events criteria and compared to published data on TOC-associated GI toxicity. Patients receiving TOC while undergoing abdominal RT had significantly increased rates of any grade of diarrhea (p = 0.002), hyporexia (p = 0.0045), and vomiting (p = 0.003), as well as severe hyporexia (p = 0.003) when compared across the treatment groups. This retrospective study reveals significantly increased incidences of GI toxicity when abdominal RT is combined with TOC in canine patients. These findings are in-line with the clinical concerns reported for increased normal tissue toxicity in human patients when antiangiogenics are combined with RT.

中文翻译：

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接受同时腹部放射治疗和磷酸托瑟尼布治疗的犬癌患者的胃肠道毒性发生率增加

受体酪氨酸激酶抑制剂 (TKI) 用于治疗人类和犬类癌症，由于其抗癌和抗血管生成作用，可与放射治疗 (RT) 联合使用以增强对肿瘤的控制；然而，最近出现的病例报告描述了在人类癌症患者中，当抗血管生成治疗与大分割放射治疗相结合时，胃肠道毒性的发生率。我们评估了接受同时接受大分割腹部放疗和 TKI 托塞尼布 (TOC) 的狗与单独接受腹部放疗、单独 TOC 或同时接受非腹部放疗和 TOC 的狗的胃肠道 (GI) 毒性发生率。对犬癌患者的医疗记录进行了回顾性审查，并将确定的犬纳入以下治疗类别：部分腹部接受放疗并同时接受 TOC (n = 19)、仅接受腹部 RT (n-29)、仅接受 TOC (n = 20) 或非腹部 RT 加 TOC (n = 9) 的狗。使用兽医合作肿瘤学组 - 不良事件通用术语标准对毒性进行分级，并与已发表的 TOC 相关胃肠道毒性数据进行比较。在接受腹部放疗期间接受 TOC 的患者，任何级别的腹泻 (p = 0.002)、缺食 (p = 0.0045) 和呕吐 (p = 0.003) 以及严重缺食 (p = 0.003) 的发生率均显着增加。治疗组。这项回顾性研究表明，在犬科患者中，腹部放疗与 TOC 联合使用会显着增加胃肠道毒性的发生率。