关键词: USMB bleomycin companion animals contrast-enhanced ultrasound feline head and neck cancer oral squamous cell carcinoma veterinary medicine

来  源:   DOI:10.3390/pharmaceutics15041166   PDF(Pubmed)

Abstract:
To investigate the feasibility and tolerability of ultrasound and microbubbles (USMB)-enhanced chemotherapy delivery for head and neck cancer, we performed a veterinary trial in feline companion animals with oral squamous cell carcinomas. Six cats were treated with a combination of bleomycin and USMB therapy three times, using the Pulse Wave Doppler mode on a clinical ultrasound system and EMA/FDA approved microbubbles. They were evaluated for adverse events, quality of life, tumour response and survival. Furthermore, tumour perfusion was monitored before and after USMB therapy using contrast-enhanced ultrasound (CEUS). USMB treatments were feasible and well tolerated. Among 5 cats treated with optimized US settings, 3 had stable disease at first, but showed disease progression 5 or 11 weeks after first treatment. One cat had progressive disease one week after the first treatment session, maintaining a stable disease thereafter. Eventually, all cats except one showed progressive disease, but each survived longer than the median overall survival time of 44 days reported in literature. CEUS performed immediately before and after USMB therapy suggested an increase in tumour perfusion based on an increase in median area under the curve (AUC) in 6 out of 12 evaluated treatment sessions. In this small hypothesis-generating study, USMB plus chemotherapy was feasible and well-tolerated in a feline companion animal model and showed potential for enhancing tumour perfusion in order to increase drug delivery. This could be a forward step toward clinical translation of USMB therapy to human patients with a clinical need for locally enhanced treatment.
摘要:
探讨超声和微泡(USMB)增强化疗治疗头颈部恶性肿瘤的可行性和耐受性。我们在患有口腔鳞状细胞癌的猫科动物中进行了一项兽医试验.六只猫接受了博来霉素和USMB联合治疗三次,在临床超声系统和EMA/FDA批准的微泡上使用脉搏波多普勒模式。对他们的不良事件进行了评估,生活质量,肿瘤反应和存活率。此外,使用超声造影(CEUS)在USMB治疗前后监测肿瘤灌注.USMB治疗是可行的且耐受性良好。在5只接受美国优化设置治疗的猫中,3起初病情稳定,但在首次治疗后5或11周显示疾病进展。一只猫在第一次治疗后一周出现进行性疾病,此后保持疾病稳定。最终,除了一只猫,所有的猫都表现出进行性疾病,但每个人的存活时间都比文献报道的中位总生存时间44天更长.在USMB治疗之前和之后立即进行的CEUS表明,在12个评估的治疗阶段中,有6个评估的曲线下面积(AUC)增加,肿瘤灌注增加。在这个产生假设的小型研究中,USMB加化疗在猫伴侣动物模型中是可行的并且耐受性良好,并且显示出增强肿瘤灌注以增加药物递送的潜力。这可能是朝着将USMB疗法临床转化为临床需要局部增强治疗的人类患者迈出的一步。
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