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1.
Lessons Learned
  • SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
  • This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
  • SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.
BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m2 to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m2 cohort; grade 3 gastric hemorrhage in the 6.5 mg/m2 cohort; grade 2 thromboembolic event in the 24 mg/m2 cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m2 cohort. The MTD was 24 mg/m2, and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m2 every 21 days; it is safe and tolerable in patients with solid tumors.  相似文献   
2.
3.

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Methods

Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.

Results

In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.

Conclusions

Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection.  相似文献   
4.

Purpose

To evaluate the feasibility of a same-day yttrium-90 (90Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

Materials and Methods

All same-day radioembolization procedures performed over 1 y (February 2017 to January 2018) were included in this single-institutional retrospective analysis, in which 34 procedures were performed in 26 patients (median age, 63 y; 13 women), 19 with liver metastases and 7 with HCC. Yttrium-90 treatment activities were calculated by body surface area method. Tumor imaging response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for liver metastases and modified RECIST for HCC. Clinical side effects and adverse events were graded per Common Terminology Criteria for Adverse Events version 4.0.

Results

All planned cases were technically successful, and no cases were canceled for elevated LSF or vascular anatomic reasons. Pretreatment angiography modified the planned 90Y treatment activity in 1 case in which vascular anatomy required a lobar-dose split into 2 for segmental infusions. In 18% of cases, patients were briefly admitted after the procedure for observation or symptom management. Imaging evaluation of initial efficacy at 1 month demonstrated partial response in 25% and stable disease in 67% of patients with liver metastases and partial/complete response in 43% and stable disease in 14% of patients with HCC. Grade ≥ 3 adverse events occurred in 6% of cases, with no systemic therapy–limiting toxicities. The mean total procedure time was 4.2 hours.

Conclusions

A same-day 90Y radioembolization protocol with resin microspheres is feasible in select patients, which can expedite cancer therapy.  相似文献   
5.
静脉输液滴速自动显示仪的研制   总被引:3,自引:3,他引:0  
本文介绍了该产品基于数字电路和基于单片机ATMEL89C2051两种方案软硬件设计。能够正确显示静脉输液滴数,方便患者和减轻陪护人员的负担,并且在无药液和血管堵塞两种情况下,自动报警。在输液过程中,发光二极管同步显示液滴滴速快慢的变化。  相似文献   
6.
便携式多普勒血管探测仪在皮瓣移植中的应用   总被引:3,自引:0,他引:3  
目的 :研究皮瓣移植前简单、可靠的血管探测的方法。方法 :在皮瓣移植前 ,以 HADECO ES-1 0 0 0 SPM多普勒血管探测仪对皮瓣血管蒂及皮动脉进行探测 ,与术中皮动脉探查结果进行比较 ,考察术前血管探测的准确性和意义。结果 :皮瓣血管蒂及皮动脉术前探测与术中探查结果完全一致。结论 :便携式血管多普勒仪是皮瓣移植前 ,简单、可靠的血管探测的仪器 ,根据探测结果进行皮瓣设计 ,有效地降低了手术失败的风险  相似文献   
7.
目的建立一种操作简便、高效的测定脑组织中去甲肾上腺素(NA)、肾上腺素(AD)、多巴胺(DA)、3,4二羟基苯乙酸(DOPAC)及高香草酸(HVA)的方法,为有关药物作用机理的研究提供实验手段.方法以有机溶剂提取,高效液相色谱--电化学检测器(HPLC-EC)测定大鼠纹状体、皮质、下丘脑NA、AD、DA、DOPAC及HVA的含量.结果测得NA、AD、DA、DOPAC及HVA的绝对回收率依次分别为:80.3%±12.4%,86.5%±14.3%,90.3%±12.1%,89.5%±17.2%、87.6%±[13].2%.线性范围0.2~20ng,批内与批间变异系数分别小于8%及10%.结论该方法具有简便、迅速、回收率较高的特点,便于实验室应用.  相似文献   
8.
For some disabled people pointing provides a more convenient means of communication and control than the use of switches. The quadriplegic who retains good control of head movement can be provided with a number of input alternatives, but no existing system meets all the requirements of a general-purpose electronic pointing device. Consequently the Oxford Optical Pointer has been developed. The principle by which it converts relative direction into analogue electrical signals is described and its application as a head-mounted device for controlling an electric wheelchair is presented.  相似文献   
9.
目的:确定多层螺旋CT肝门静脉系统检查的合理延迟时间及双通路注射对比剂法的可行性。方法:分为2个步骤研究:①随机选择无腹部及心血管疾患的患者53例,以3 ml/s速率注射造影剂20 ml,行同层动态扫描,计算腹主动脉、肝门静脉、下腔静脉、肝实质的对比剂时间密度曲线,及它们的相关性。②47例需门静脉检查的患者,行MDCT肝区移床式、动态扫描,在右肘部静脉及下肢静脉同时注入对比剂,对比剂总量1.5~2 ml/kg。扫描时使用对比剂自动示踪软件,设动脉血管阈值为120 HU启动扫描,动脉期扫描完成后延时20.1±5.54 s行门静脉扫描,分别评价肝门静脉、肝静脉、下腔静脉的显示率及程度。结果:①20 ml对比剂注射同层动态扫描肝门层面腹主动脉达峰时间为18.5±4.81 s,肝门静脉达峰时间是38.61±6.59 s,下腔静脉达峰时间是55.44±12.16 s,肝实质的达峰时间是56±5.7 s。②肝门静脉显示率达100%,肝门静脉主干等显示程度平均评分2.50~2.93;相关小分支静脉显示率为87%~98%,显示平均评分2.25~2.63。结论:MDCT右肘部静脉及下肢静脉同时注入对比剂,在动脉期扫描完成后,延时20.1±5.54 s行肝门静脉检查,肝门静脉系统成像效果良好。  相似文献   
10.
麻醉剂量羟甲芬太尼对大鼠脑内单胺递质及其代谢物含量的影响金昔陆1唐琴梅金文桥周德和李桂芬池志强(中国科学院上海药物研究所,上海200031)羟甲芬太尼(ohmefentanyl,OMF)是一种新的高选择性高亲和力μ阿片受体激动剂,在动物中能产生麻醉作...  相似文献   
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