Leblanc Amy K, Miller Ashley N, Galyon Gina D, Moyers Tamberlyn D, Long Misty J, Stuckey Alan C, Wall Jonathan S, Morandi Federica
Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA.
Vet Radiol Ultrasound. 2012 May-Jun;53(3):348-57. doi: 10.1111/j.1740-8261.2012.01925.x. Epub 2012 Feb 24.
Palladia(TM) (toceranib phosphate-Pfizer Animal Health) is a novel orally administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor growth, progression, and metastasis. Toceranib's targets include vascular endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth factor receptor, and kit. Positron Emission Tomography/Computed Tomography (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to antineoplastic therapy in human patients. In this study, serial PET/CT imaging with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing dogs underwent tumor assessment using both standard RECIST criteria and PET/CT prior to and at a median of 5 weeks postinitiation of toceranib treatment. Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with subsequent modifications based on observed toxicity. Treatment was continued in patients achieving stable disease with acceptable drug tolerance. One dog was maintained on drug despite dose modification due to toxicity; measurable clinical and image-based responses were seen after 10 weeks of therapy. All others had stable or progressive disease based on clinical restaging and PET/CT at first recheck. . Due to discordance with anatomic and metabolic imaging, further studies are needed to investigate the role of molecular imaging in assessment of drug response and identify other potential molecular targets of toceranib.
帕拉迪(Palladia™)(磷酸托西替尼,辉瑞动物健康公司生产)是一种新型口服受体酪氨酸激酶抑制剂(TKI),已被批准用于治疗犬肥大细胞瘤。受体酪氨酸激酶失调会导致肿瘤生长、进展和转移。托西替尼的靶点包括血管内皮生长因子受体(VEGFR - 2/Flk - 1/KDR)、血小板衍生生长因子受体和干细胞生长因子受体(Kit)。正电子发射断层扫描/计算机断层扫描(PET/CT)通常用于诊断、预测和监测人类患者对抗肿瘤治疗的反应。在本研究中,使用(18)F - 氟脱氧葡萄糖((18)FDG)进行连续PET/CT成像,以评估可测量实体恶性肿瘤犬对托西替尼治疗的反应。6只荷瘤犬在开始托西替尼治疗前及治疗开始后中位时间5周时,使用标准RECIST标准和PET/CT进行肿瘤评估。托西替尼最初的给药目标剂量为3.25 mg/kg口服,每48小时一次,随后根据观察到的毒性进行调整。对于疾病稳定且药物耐受性可接受的患者继续进行治疗。1只犬尽管因毒性进行了剂量调整,但仍继续用药;治疗10周后可见可测量的临床和基于图像的反应。在首次复查时,根据临床再分期和PET/CT,所有其他犬的疾病均稳定或进展。由于解剖学和代谢成像结果不一致,需要进一步研究以探讨分子成像在评估药物反应中的作用,并确定托西替尼的其他潜在分子靶点。