Yu Tinghe, Luo Li, Wang Li
a Chongqing Medical University, The Second Affiliated Hospital, Key Medical Laboratory of Obstetrics and Gynecology , Chongqing 400010, China
Expert Opin Drug Deliv. 2016;13(1):37-47. doi: 10.1517/17425247.2015.1083008. Epub 2015 Aug 25.
The use of ultrasound to sensitize chemotherapy has been explored, a large amount of encouraging preclinical data has been reported, and an increase in drug influx is considered the main mechanism, leading scientists to believe that ultrasonic chemotherapy will change clinical practice.
Here we first outline the clinical efficacy of ultrasonic chemotherapy using data from controlled trials of high-intensity focused ultrasound (HIFU)-chemotherapy, and then discuss the gap between laboratory and bedside. Data from clinical trials showed that focused ultrasound enhanced anticancer drugs in only 35.0% (7/20) of trials. Preclinical trials indicate that ultrasound augments the action of drugs via multiple pathways. The effect of a transient increase in the intracellular drug level due to ultrasound can be counteracted by certain cellular factors, causing a lack of chemosensitization. The experimental method used can lead to biases in preclinical trials.
Chemotherapy should not be recommended in HIFU treatments at present. The use of HIFU-chemotherapy in digestive-tract cancers can provide feedback for preclinical and translational researches in ultrasonic chemotherapy. The clinical relevance of preclinical trials should be improved; the drug-ultrasound interactions, sequence effects, predictiveness of in vivo models, and adjuncts of ultrasonic sensitization should be particularly considered.
人们已经探索了利用超声使化疗增敏的方法,已报道了大量令人鼓舞的临床前数据,药物流入增加被认为是主要机制,这使得科学家们相信超声化疗将改变临床实践。
在此,我们首先利用高强度聚焦超声(HIFU)化疗对照试验的数据概述超声化疗的临床疗效,然后讨论实验室与临床应用之间的差距。临床试验数据表明,在仅35.0%(7/20)的试验中聚焦超声增强了抗癌药物的效果。临床前试验表明,超声通过多种途径增强药物作用。超声导致的细胞内药物水平短暂升高的效果可能会被某些细胞因子抵消,从而导致化疗增敏作用缺失。所采用的实验方法可能会导致临床前试验出现偏差。
目前在HIFU治疗中不建议进行化疗。HIFU化疗在消化道癌症中的应用可为超声化疗的临床前和转化研究提供反馈。应提高临床前试验的临床相关性;尤其应考虑药物 - 超声相互作用、序列效应、体内模型的预测性以及超声增敏的辅助手段。