A randomized Phase III trial of neoadjuvant recombinant human endostatin,docetaxel and epirubicin as first‐line therapy for patients with breast cancer (CBCRT01)

To further assess the efficacy and safety of recombinant human endostatin (rh‐endostatin), a Phase III, multicenter, prospective, randomized, controlled clinical trial was conducted. Patients to be treated with neoadjuvant docetaxel and epirubicin (DE) or DE plus rh‐endostatin (DEE) were eligible for this trial. The primary endpoint was clinical/pathological response. Secondary endpoints included adverse events and quality of life (QOL). Finally, 803 patients were enrolled and randomly assigned to receive DE (n = 402) or DEE (n = 401) regimen. After three cycles of neoadjuvant therapy, “complete response” achieved in 14.2% of patients in DEE group versus 6.7% in DE group, “partial response” achieved in 76.8% versus 71.1%, while “stable disease” in 6.0% versus 18.9%, “progressive disease” in 3.0% versus 3.2% of patients. The rate of objective response in DEE and DE group was 91.0% and 77.9%, respectively (p < 0.001). In spite of a relatively higher pathological complete response achieved following the combination therapy, no significant difference was found between two arms. Adverse events were mostly of Grades 1–2. No significant difference in adverse event and QOL was found between the two arms. In conclusion, the combination of chemotherapy and rh‐endostatin achieved better outcomes than chemotherapy alone, and thus can be considered as a promising therapeutic strategy for breast cancer.     

N-Butyl-2-cyanoacrylate-based injectable and in situ-forming implants for efficient intratumoral chemotherapy

The local delivery of chemotherapeutic drugs to tumor sites is an effective approach for achieving therapeutic drug concentrations in solid tumors. Injectable implants with the ability to form in situ represent one of the most promising technologies for intratumoral chemotherapy. However, many issues must be resolved before these implants can be applied in clinical practice. Herein, we report a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA) and ethyl oleate, and the sol–gel phase transition is activated by anions in body fluids or blood. This newly developed injectable NBCA ethyl oleate implant (INEI) is biodegradable, biocompatible, and non-toxic. INEI solidifies in several seconds after exposure to body fluids or blood, and the implant’s in vivo degradation time can be controlled. In addition, the pore sizes formed by the polymerization of NBCA can be decreased by increasing the NBCA concentration in the implants. Therefore, the drug retention/release time can be adjusted from a few weeks to several months by changing the concentration of NBCA in the implant formulation. Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human breast cancer cells by the paclitaxel-loaded INEI (40% NBCA) was 80%, and they also indicated that tumors in some of the mice were completely eliminated by just a single dosage injection. For the epirubicin-loaded INEI (50% NBCA), the average growth inhibition rate of xenografted human liver cancer cells was 58%. Thus, the chemotherapeutic drug-loaded INEIs exhibited excellent therapeutic efficacy for local chemotherapy.     

Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells

Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor‐suppressing. Thus we studied MDA‐MB‐231 and SK‐BR‐3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI‐triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria. This inhibition increased mitochondrial cytochrome C release which augmented epirubicin‐induced caspase‐dependent apoptosis and cytotoxicity. In addition, the lysosomal neutralizing agent ammonia chloride (AC), and Atg7 knockdown by siRNA, could inhibit epirubicin‐triggered autophagy, enhance cytotoxicity, and increase caspase‐9‐ and caspase‐3‐dependent apoptosis. Thus, autophagy plays a prosurvival role in EPI‐treated MDA‐MB‐231 and SK‐BR‐3 cells, and autophagy inhibition can potentially reverse this effect and increase the cytotoxicity of EPI.     

表柔比星对比丝裂霉素行膀胱灌注治疗非肌层浸润性膀胱癌的系统评价

目的 系统评价表柔比星（EPI）对比丝裂霉素（MMC）行膀胱灌注治疗非肌层浸润性膀胱癌（NMIBC）的疗效和安全性。方法 计算机检索PubMed、Cochrane Library、Ovid平台生物医学数据库（OVID）、SpringerLink、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普生物医学数据库（VIP）及万方数据库中2000年1月1日—2023年2月1日发表的EPI（试验组）与MMC（对照组）治疗术后NMIBC的临床随机对照试验（RCT）,利用RevMan 5.3软件进行Meta分析。结果 共纳入14项RCTs,1 103例患者,其中试验组553例、对照组550例。试验组术后肿瘤复发率［OR＝0.52,95% CI（0.38,0.71）,P<0.000 1］、膀胱刺激征发生率［OR＝0.51,95% CI（0.32,0.81）,P＝0.004］、血尿发生率［OR＝0.47,95% CI（0.28,0.78）,P＝0.004］均显著低于对照组,但是两种药物行术后膀胱灌注的其他不良反应（肝肾损害、皮疹、恶心呕吐、尿道狭窄）发生率比较,差异无统计学意义［OR＝0.67,95% CI（0.36,1.27）,P＝0.22］。结论 使用EPI行膀胱灌注治疗NMIBC患者的临床疗效略优于MMC,但是仍需谨慎对待本次研究结果。     

两组大剂量化疗方案治疗晚期乳腺癌病例的比较

目的比较两组不同大剂量联合化疗方案对晚期乳腺癌的疗效和毒性反应.方法47例晚期乳腺癌随机分为两组,A组接受大剂量表阿霉素(HD-EPI 90 mg/m2)合并常规剂量的环磷酰胺(CTX)、5-氟脲嘧啶(5-FU),每21天重复;B组接受大剂量的顺铂(HD-DDP 100 mg/m2),联合常规剂量的足乙叶甙(Vp-16)、EPI,每28天重复.所有患者共接受化疗168周期,中位周期数3.5周期(2～6周期).结果A、B两组有效率分别为69.6%和70.8%(P>0.1),初治的有效率(75.0%,78.6%),略高于复治者(63.6%,60.0%).两组主要毒副反应为骨髓抑制,以白细胞减少为主,Ⅲ、Ⅳ度分别为26.1%、29.2%和13.0%、12.5%;胃肠道毒性为轻、中度,未见明显的心、肝、肾毒性.结论HD-EPI+CTX+5-FU及HD-DDP+Vp-16+EPI方案治疗晚期乳腺癌安全,有很好的疗效,可作为难治性晚期乳腺癌的一线方案.     

不同制剂紫杉醇联合表柔比星治疗晚期乳腺癌的临床观察

目的 探讨紫杉醇或白蛋白结合型紫杉醇联合表柔比星治疗晚期乳腺癌的临床疗效及不良反应.方法 选取62例晚期乳腺癌患者,按照随机对照双盲的原则将其分为治疗组和对照组各31例,其中治疗组采用白蛋白结合型紫杉醇(260 mg/m2)联合表柔比星(75 mg/m2)治疗,对照组采用紫杉醇(175 mg/m2)联合表柔比星(75mg/m2)治疗.治疗2个周期后,观察比较两组患者的临床疗效及不良反应发生情况.结果 治疗组的治疗总有效率93.5％(29/31)高于对照组的71.0％(22/31),差异具有统计学意义(x2=5.420,P=0.020).两组不良反应发生率比较差异无统计学意义(P＞0.05).结论 与紫杉醇联合多柔比星比较,白蛋白结合型紫杉醇联合表柔比星治疗晚期乳腺癌疗效好且不良反应可耐受.     

Chromosome instability and benefit from adjuvant anthracyclines in breast cancer

Background:

Duplication of the centromeric region of chromosome 17 (Ch17CEP) is associated with sensitivity to anthracyclines. An explanation may be chromosome instability (CIN); a frequent event in solid tumours associated with poor outcome. The predictive value of CIN seems to be drug dependent and CIN has been associated with both sensitivity and resistance to chemotherapy.

Methods:

In this study, we used fluorescent in situ hybridisation for chromosomes 1, 7, 11, 17 and 18 to identify patients with high tumour CIN% in 322 patients recruited into the BR9601 clinical trial.

Results:

High tumour CIN% was correlated to Ch17CEP (P=3.68e−7) and is associated with a reduced RFS (P=0.0011) and OS (P=0.04). Patients with high CIN had a decreased risk of death on E-CMF compared with CMF.

Conclusion:

CIN is of prognostic significance and may be of predictive value in determining anthracycline response, although further testing is required.     

右丙亚胺对表柔比星所致心脏毒性防治作用的观察

目的:观察右丙亚胺对表柔比星所致心脏毒性的防治作用。方法:对84例应用含表柔比星方案化疗的患者,以心电图作为观察指标,先单独化疗4个周期,然后将已出现心电图异常者归入右丙亚胺治疗组、心电图正常者分为单独化疗组及右丙亚胺联合化疗组继续单独化疗或用右丙亚胺联合化疗2个周期,观察心电图变化。结果:单独化疗4个周期过程中,心电图异常发生率为26.2%(22/84)。继续化疗2个周期,单独化疗组心电图异常发生率为38.7%(12/31),右丙亚胺联合化疗组心电图异常发生率为16.1%(5/31),RIDIT公式统计,u=1.977,P<0.05,差异有统计学意义;右丙亚胺治疗组有13.6%(3/22)患者异常心电图转为正常,有18.2%(4/22)患者异常心电图保持稳定,其余68.2%患者心脏损害加重。结论:右丙亚胺对表柔比星所致心脏毒性的发生有一定的防护作用,并且对已经形成的损害有一定的治疗作用。     

右丙亚胺对于表阿霉素心脏毒性的保护作用

目的:观察右丙亚胺（dexrazoxane,DEX）对表阿霉素（EPI）辅助化疗时的心脏保护作用。方法:随机将来我院治疗的女性乳腺癌患者分为观察组和对照组,两组患者均采用EPI为主的术后辅助化疗方案,观察组在EPI为主的化疗方案基础上加用DEX（DEX∶EPI＝10∶1）,在第1次应用EPI时即给予DEX。采用心肌钙蛋白T（cTnt)和左心室射血分数（LVEF）监测治疗前、治疗第1和第3个周期、治疗完成时、完成后半年、1年的心脏功能状态,同时观察治疗的非心脏毒性。结果:两组患者在年龄、体重、ECOG评分和分期方面没有统计学差异（P>0.05）。EPI治疗第1个周期开始cTnt明显上升,到治疗结束时达到最高,直到治疗后1年仍然维持在较高水平;加用DEX组在治疗期间及治疗后cTnt水平都较低;而LVEF在两组的各个治疗阶段水平都没有统计学差异（P>0.05）;两组的非心脏不良反应没有差异。结论:EPI从第1次应用时对心脏就产生了明显的毒性,加用DEX可以降低这种心脏毒性。     

Epirubicin Inhibits Soluble CD25 Secretion by Treg CellsIsolated from Diffuse Large B-cell Lymphoma Patients

Objective: To investigate the effect of epirubicin on soluble CD25 (sCD25) secretion by CD4+CD25+regulatory T (Treg) cells isolated from diffuse large B-cell lymphoma (DLBCL) patients. Methods: Treg cellswere isolated from the peripheral blood mononuclear cells isolated from the newly diagnosed DBLCL patients.The concentration of sCD25 in the supernatant was determined with a commercial sCD25 (IL-2R) enzyme-linkedimmunosorbent assay (ELISA) kit. The fluorescence intensity of CD25 was detected by flow cytometry. Results:Cell survival rate was significantly decreased along with the increase of epirubicin concentration after treatmentfor 24 h. There was also a significant difference in the concentration of sCD25 between the epirubicin group andthe control group (P<0.01). A positive correlation between the Treg cells survival rate and the concentration ofsCD25 was detected (r=0.993, P<0.01). When equal numbers of CD4+CD25+ Treg cells of the epirubicin groupand the control group were cultured for another 24 h without epirubicin the CD25 fluorescence intensity onthe surface of Treg cells was obviously higher in the epirubicin group than that in the control group (P<0.01),while the sCD25 concentration in the supernatant in the epirubicin group was significantly lower than that inthe control group (P<0.05). Conclusion: Epirubicin may improve the body’s immune functions by inhibiting thesCD25 secretion by Treg cells in DLBCL patients.