Castle Jason, Kotopoulis Spiros, Forsberg Flemming
General Electric Research, Niskayuna, NY, USA.
National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
Methods Mol Biol. 2020;2059:191-205. doi: 10.1007/978-1-4939-9798-5_9.
Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than 53,000 new cases in 2017. It is the fourth leading cause of cancer-related death in both men and women. Nonetheless, there has been no significant improvement in survival for pancreatic ductal adenocarcinoma (PDAC) patients over the past 30+ years. For this reason, there is a considerable and urgent clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, resulting in improved outcomes for patients with PDAC.This chapter describes the development of contrast-enhanced ultrasound image-guided drug delivery (CEUS-IGDD or sonoporation) to be that method and to translate it from the lab to the clinic. The initial clinical focus has been on a Phase I clinical trial for enhancing the effectiveness of standard chemotherapeutics for treatment of inoperable PDAC, which demonstrated a median survival increase from 8.9 months to 17.6 months in ten subjects augmented with sonoporation compared to 63 historical controls (p = 0.011). Recent efforts to optimize this platform and move forward to a larger Phase II clinical trial will be described.
胰腺癌是美国诊断出的第三大常见癌症,2017年新增病例超过53000例。它是男性和女性癌症相关死亡的第四大主要原因。尽管如此,在过去30多年里,胰腺导管腺癌(PDAC)患者的生存率并未得到显著改善。因此,迫切需要开发创新策略以实现有效的药物递送和治疗监测,从而改善PDAC患者的治疗效果。本章介绍了超声造影图像引导药物递送(CEUS-IGDD或声穿孔)的发展情况,将其作为一种方法,并将其从实验室转化到临床应用。最初的临床重点是一项I期临床试验,旨在提高标准化疗药物治疗无法手术的PDAC的有效性,与63例历史对照相比,在10例接受声穿孔增强治疗的受试者中,中位生存期从8.9个月增加到17.6个月(p = 0.011)。本文还将介绍近期为优化该平台并推进更大规模的II期临床试验所做的努力。