Ferrero Simone, Leone Roberti Maggiore Umberto, Aiello Nicoletta, Barra Fabio, Ditto Antonino, Bogani Giorgio, Raspagliesi Francesco, Lorusso Domenica
a Academic Unit of Obstetrics and Gynaecology , IRCCS AOU San Martino - IST , Genova , Italy.
b Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) , University of Genoa , Genoa , Italy.
Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):881-889. doi: 10.1080/17425255.2017.1351943. Epub 2017 Jul 13.
Uterine leiomyosarcomas (ULMS) represent 1.3% of all uterine malignant tumors. Surgery is the curative treatment for patients with early stage disease. In case of advanced, persistent or recurrent tumor, chemotherapy represents the standard of care, but these patients have a poor prognosis. As the results with available therapies are far from being satisfactory, research is focusing on identification of new compounds. In 2012 the Food and Drug Administration (FDA) licensed pazopanib for the treatment of advanced soft-tissue sarcomas failing previous chemotherapy. Areas covered: The aim of this article is to review the literature on the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of the tyrosine kinase inhibitor (TKI), pazopanib in the treatment of ULMS. Expert opinion: The discovery of some relevant signalling pathways in LMS cells led to the development of new targeted drugs with promising results in the management of these tumors. Pazopanib is a multi-target second-generation TKI with activity against growth factors involved in angiogenesis. It has shown promising results both in terms of efficacy and safety, as shown in the EORTC 62043 Study and the PALETTE trial. Further studies are awaited to evaluate its efficacy in uterine leiomyosarcomas.
子宫平滑肌肉瘤（ULMS）占所有子宫恶性肿瘤的1.3%。手术是早期疾病患者的治愈性治疗方法。对于晚期、持续性或复发性肿瘤患者，化疗是标准治疗方法，但这些患者预后较差。由于现有治疗方法的效果远不能令人满意，研究正集中在新型化合物的鉴定上。2012年，美国食品药品监督管理局（FDA）批准帕唑帕尼用于治疗既往化疗失败的晚期软组织肉瘤。涵盖领域：本文旨在综述酪氨酸激酶抑制剂（TKI）帕唑帕尼治疗ULMS的药代动力学、药效学、临床疗效和安全性方面的文献。专家观点：在平滑肌肉瘤细胞中发现了一些相关信号通路，从而开发出了新的靶向药物，在这些肿瘤的治疗中取得了有前景的结果。帕唑帕尼是一种多靶点第二代TKI，对参与血管生成的生长因子具有活性。如欧洲癌症研究与治疗组织（EORTC）62043研究和PALETTE试验所示，它在疗效和安全性方面均显示出有前景的结果。有待进一步研究以评估其在子宫平滑肌肉瘤中的疗效。
