Musser Margaret L, Taikowski Kathryn L, Johannes Chad M, Bergman Philip J
VCA Veterinary Referral and Emergency Center, Norwalk, CT, USA.
Present address: Iowa State University College of Veterinary Medicine, Ames, IA, USA.
BMC Vet Res. 2018 Sep 3;14(1):272. doi: 10.1186/s12917-018-1597-7.
Effective treatment options for inoperable, metastatic, or recurrent canine pheochromocytomas are lacking. In humans, specific germline mutations exist that drive the development of pheochromocytomas. Pharmaceutical blockade of these abnormalities with small molecule inhibitors are an effective treatment strategy. Similar mutations may exist in the dog, and thus, treatment with similar small molecule inhibitors may provide a survival advantage. The purpose of this study was to assess the role of toceranib phosphate in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas.
Retrospectively, medical records of dogs that had a diagnosis or suspect diagnosis of a pheochromocytoma were reviewed for information regarding response to toceranib phosphate and overall outcome. Five dogs were identified that fit the inclusion criteria. All five experienced clinical benefit (1 partial response, 4 stable disease). Progression-free interval (PFI) for the dog with the partial response was 61 weeks. PFI for the two dogs with stable measurable disease were 36 weeks and 28 weeks. PFI in the two dogs with stable metastatic disease were at least 11 weeks and 18 weeks.
Based on this limited series of dogs, the results suggest that toceranib may have biological activity in dogs with primary and metastatic pheochromocytomas. Larger studies are needed to define the use and response to toceranib in dogs with gross, microscopic, and metastatic pheochromocytoma.
对于无法手术切除、转移性或复发性犬嗜铬细胞瘤,缺乏有效的治疗选择。在人类中,存在特定的种系突变驱动嗜铬细胞瘤的发生。用小分子抑制剂对这些异常进行药物阻断是一种有效的治疗策略。狗身上可能存在类似的突变,因此,用类似的小分子抑制剂进行治疗可能会带来生存优势。本研究的目的是评估磷酸托西拉尼在治疗无法手术切除、转移性或复发性犬嗜铬细胞瘤中的作用。
回顾性地审查了诊断或疑似诊断为嗜铬细胞瘤的犬只的病历,以获取有关对磷酸托西拉尼的反应和总体结果的信息。确定了五只符合纳入标准的狗。所有五只狗均有临床获益(1例部分缓解,4例病情稳定)。部分缓解的狗的无进展生存期(PFI)为61周。病情稳定且可测量的两只狗的PFI分别为36周和28周。病情稳定的转移性疾病的两只狗的PFI至少为11周和18周。
基于这一有限的犬只系列,结果表明磷酸托西拉尼可能对原发性和转移性嗜铬细胞瘤犬具有生物学活性。需要进行更大规模的研究来确定磷酸托西拉尼在患有肉眼可见、显微镜下可见和转移性嗜铬细胞瘤的犬只中的使用方法和反应。