多西紫杉醇作为晚期非小细胞肺癌的二线治疗药物的系统评价

目的系统评价多西紫杉醇作为晚期非小细胞肺癌二线治疗药物的疗效、不良反应、生存质量及给药方案。方法电子检索Medline（1991～2008．2）、Pubmed、CBMDisc等数据库，对符合纳入标准的研究，采用RevMan4．2软件进行Meta分析。结果共有8篇文献纳入研究。多西紫杉醇治疗晚期非小细胞肺癌疗效与支持性疗法相比，疾病进展期和中位生存期明显延长，分别是10．6周和6．7周（P〈0．001）、7．0月和4．6月（P〈0．001），1年生存率分别为37％和11％。不良反应研究中，3—4级血液学不良反应在多西紫杉醇组中发生率较高，其中高剂量组（100mg／m^2）发生率高于低剂量组（75mg／m^2）；3～4级非血液学不良反应，多西紫杉醇组和支持治疗组发生率相似。另外以长春瑞滨或异环磷酰胺为对照的研究显示，多西紫杉醇组反应率、疾病进展时间和生存率优于对照；4级血液学不良反应多西紫杉醇组高于对照组，其他3～4级非血液学不良反应的发生率无明显规律。生存质量评价（LCSS、QLQ—C30或QLQ—LC13）方面，患者自评和观察者评价均显示多西紫杉醇组优于支持治疗组。不同给药方案（3周给药和1周给药）的Meta分析结果可以看出不同给药方案在疾病控制率、反应率及1年生存率方面没有统计学差异（P〉0．05）；在嗜中性白细胞减少症、白细胞减少症的发生率上，1周给药组发生率均低于3周给药组（P〈0．01）；在非血液学不良反应如虚弱、恶心／呕吐的发生率上，不同给药方案没有统计学差异（P〉0．5）。结论多西紫杉醇可以认为是在晚期非小细胞肺癌的二线治疗中疗效确切的药物；不同的多西紫杉醇给药方案（3周vs1周），在疗效方面差异不明显，在不良反应发生率上略有差异，因此，在发生严重血液学不良反应的情况下，可以用1周给药代替3周给药进行治     

参丹活血胶囊联合DP方案治疗不可切除的老年晚期卵巢腺癌的临床研究

目的探讨参丹活血胶囊联合DP方案(多西他赛注射液和顺铂注射液)治疗不可切除的老年晚期卵巢腺癌的临床疗效。方法选取2016年1月—2017年5月绵阳市中心医院收治的不可切除的老年晚期卵巢腺癌患者82例为研究对象,采用随机数字表法将所有患者分为对照组和治疗组,每组各41例。对照组患者给予DP方案治疗,第1天静脉滴注多西他赛注射液,75 mg/m2;第1~3天静脉滴注顺铂注射液,70 mg/m2。治疗组在对照组治疗的基础上口服参丹活血胶囊,6粒/次,3次/d。每个疗程3周,两组患者均连续治疗4个疗程。评价两组患者近期临床疗效,同时比较治疗前后的生活质量评分、免疫功能指标和毒副反应。结果治疗后,对照组和治疗组的客观缓解率分别为60.9%、78.0%,疾病控制率分别为43.9%、58.5%,两组近期临床疗效比较差异有统计学意义(P0.05)。治疗后,两组功能状况评分、社会状况评分均显著升高,附加关注评分、情感状况评分、生理状况评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组生活质量评分改善情况明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、CD3~+和CD4~+均显著增高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组免疫指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。治疗期间,治疗组各项毒副反应发生率均显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论参丹活血胶囊联合DP方案治疗不可切除的老年晚期卵巢癌具有较好的临床疗效,能够有效改善患者生活质量和免疫功能,毒副作用小,具有一定的临床推广应用价值。     

多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究

背景与目的：乳腺癌患者体内存在严重的免疫失衡,胸腺肽α1（thymosin α1,Tα1）作为免疫增强剂发挥作用,探究多西他赛（docetaxel,DCT）联合Tα1对大鼠乳腺癌免疫微环境中调节性T细胞（regulatory T cell,Treg）数量的影响,并初步分析其作用机制。方法：随机将60只雌性SD大鼠分为模型组、DCT组（剂量为10 mg/kg）、Tα1组（剂量为0.8 mg/kg）及3个DCT+Tα1组（DCT剂量为10 mg/kg,Tα1剂量分别为0.2、0.4、0.8 mg/kg）,每组10只。给雌性SD大鼠接种大鼠乳腺癌细胞系SHZ-88建立移植瘤模型,成瘤后,DCT组、Tα1组及DCT+Tα1组分别腹腔注射相应剂量的DCT、Tα1,给药周期均为20 d,1次/d。测量大鼠肿瘤体积,采用原位末端转移酶标记（TdT-mediated dUTP nick end labeling,TUNEL）染色法检测肿瘤细胞的凋亡情况。采用流式细胞术检测大鼠肿瘤组织中CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Treg数量及表达程序性死亡［蛋白］-1（programmed death-1,PD-1）的Treg数量,采用酶联免疫吸附试验（enzyme-linked immunosorbent assay,ELISA）检测肿瘤组织中白细胞介素-10（interleukin-10,IL-10）、转化生长因子-β（transforming growth factor-β,TGF-β）的表达,采用蛋白质印迹法（Western blot）检测肿瘤组织中PD-1及程序性死亡［蛋白］配体-1（programmed death ligand-1,PD-L1）的表达。结果：与模型组相比,给药组均可明显抑制肿瘤的生长,促进肿瘤细胞凋亡,显著下调CD4 ^＋CD25 ^＋ Foxp3 ^＋ Treg数量,以及IL-10、TGF-β、PD-1和PD-L1的表达（P ＜ 0.05）,其中DCT+0.8 mg/kg Tα1组作用效果最显著,明显优于其他给药组。结论：DCT联合Tα1可抑制大鼠肿瘤的生长,其中以DCT+0.8 mg/kg Tα1效果最显著,作用机制可能是通过下调PD-1/PD-L1的表达,抑制CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Treg浸润。     

Metastatic hormone-sensitive prostate cancer: How should it be treated?

The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years. The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel, abiraterone acetate, enzalutamide, apalutamide, and/or radiotherapy to the primary tumour. As a result, these approaches are now included in treatment guidelines and considered standard of care. However, the different treatment strategies have not been directly compared, and thus treatment selection remains at the discretion of the individual physician or, ideally, a multidisciplinary team. Given the range of available treatment approaches with varying toxicity profiles, treatment selection should be individualized based on the patient’s clinical characteristics and preferences, which implies active patient participation in the decision-making process. In the present document, we discuss the changing landscape of the management of patients with metastatic hormone-sensitive prostate cancer in the context of several recently-published landmark randomized trials. In addition, we discuss several unresolved issues, including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.     

A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer

IntroductionChemotherapy eliminates most of the cancer cells except those with potential for self-renewal and tumor initiation, called cancer stem cells (CSCs). Chloroquine, through bioinformatics, was found to be a potential agent to target CSCs. We designed a phase II trial to test the efficacy and safety of chloroquine in combination with taxane or taxane-like chemotherapy agents in patients with advanced or metastatic breast cancer who are refractory to anthracycline-based chemotherapy.Patients and MethodsFemale patients ≥ 18 years of age who had received prior anthracycline chemotherapy were enrolled in this study. Chloroquine 250 mg was given daily orally with either docetaxel or paclitaxel or nab-paclitaxel or ixabepilone every 3 weeks. The maximum number of 3-week cycles allowed was 6. The primary efficacy endpoint was the objective response rate (ORR). The secondary efficacy endpoints included progression-free survival (PFS) and safety analysis.ResultsThirty-eight patients were enrolled in the study, and 31 patients were evaluated for response. The median age was 54.1 years (range, 31.7-78.1 years). The ORR was 45.16% (95% confidence interval [CI], 29.2%-62.2%), which was higher than the expected ORR of 30% (P = .03). Patients were followed for a median of 25.4 months and experienced a median PFS of 12.4 months (95% CI, 4.9-24.6 months) and a median OS of 25.4 months (95% CI, 13.7-83.5 months). The combination was well-tolerated, with only 13.15% of patients experiencing grade ≥ 3 adverse events.ConclusionA combination of chloroquine with taxane or taxane-like chemotherapy was efficacious in patients with locally advanced or metastatic breast cancer with prior anthracycline-based chemotherapy.     

A comparison between raltitrexed plus cisplatin and docetaxel plus cisplatin in concurrent chemoradiation for non-surgical esophageal squamous cell carcinoma

PurposeChemoradiotherapy (CRT) is considered as a standard treatment for unresectable and inoperable esophageal cancer (EC) patients. However, no consensus has been reached regarding the optimal synchronous chemotherapy regimen and the best combination of radiotherapy and chemotherapy. The aim of this study was to evaluate the efficacy and toxicity of raltitrexed plus cisplatin and docetaxel plus cisplatin to find a safe and effective concurrent chemotherapy schedule.Patients and methodsOur retrospective study included 151 EC patients treated with raltitrexed and cisplatin (RP) (n = 90) or docetaxel and cisplatin (DP) (n = 61) from 2011 till 2018. Survival outcomes and treatment related toxicity were analyzed between the two groups.ResultsPFS and OS were 18 and 34 months in the RP group, while 13 and 20 months in the DP group (P = 0.118 and P = 0.270). The 1-, 2-, 3-year survival rates of the RP group were 71.1, 55.4 and 46.4%. For the DP group, these were 63.9, 44.3 and 37.6%, respectively. Compared with DP group, RP group received a superior CR rate (68.9% versus 52.5%, P = 0.041). There was a trend that the total number of toxic reactions in RP group was lower than that in DP group (P = 0.058).ConclusionsEven RP and DP groups have the similar survival outcomes and toxicity, raltitrexed/cisplatin get a higher complete response rate. Our study suggests that raltitrexed combined with cisplatin is a safe and effective concurrent chemotherapy regimen and it might be used as an alternative for cisplatin/5-FU and cisplatin/docetaxel in CCRT for EC patients.     

Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles

Hydrophobically modified glycol chitosan (HGC) nanoparticles, a new nano-sized drug carrier, were prepared by introducing a hydrophobic molecule, cholanic acid, to water soluble glycol chitosan. The HGC nanoparticles were easily loaded with the anticancer drug docetaxel (DTX) using a dialysis method, and the resulting docetaxel-loaded HGC (DTX-HGC) nanoparticles formed spontaneously self-assembled aggregates with a mean diameter of 350 nm in aqueous condition. The DTX-HGC nanoparticles were well dispersed and stable for 2 weeks under physiological conditions (pH 7.4 and 37°C) and a sustained drug release profile, in vitro. In addition, the DTX-HGC nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the DTX-HGC nanoparticles might also be stable in the blood stream. The DTX-HGC nanoparticles exhibited a distinctive deformability in aqueous conditions, in that they could easily pass through a filter membrane with 200 nm pores despite their mean diameter of 350 nm. We also evaluated the time-dependent excretion profile, in vivo biodistribution, prolonged circulation time, and tumor targeting ability of DTX-HGC nanoparticles by using a non-invasive live animal imaging technology. Finally, under optimal conditions for cancer therapy, the DTX-HGC nanoparticles showed higher antitumor efficacy such as reduced tumor volume and increased survival rate in A549 lung cancer cells-bearing mice and strongly reduced the anticancer drug toxicity compared to that of free DTX in tumor-bearing mice. Together our results showed that the anticancer loaded nano-sized drug carriers are a promising nano-sized drug formulation for cancer therapy.     

三种含铂化疗方案治疗晚期非小细胞肺癌的临床观察

目的 观察三种抗癌药(长春瑞滨、吉西他滨和多西紫杉醇)联合顺铂治疗晚期非小细胞肺癌(NSCLC)的近期疗效及毒性反应.方法 经病理组织学或细胞学证实的70例晚期NSCLC患者,随机按治疗方法 分为3组化疗,长春瑞滨联合顺铂(NP)组24例,吉西他滨联合顺铂(GP)组25例,多西紫杉醇联合顺铂(TP)组21例,3组患者资料具备可比性,3组患者采用对应药物进行治疗,均以21d为一周期,连续应用两周期后评价疗效及不良反应.结果 NP组总有效率29.2%(7/24),GP组总有效率40.0%(10/25),TP组总有效率33.3%(7/21),3组方案总有效率比较无统计学差异(P＞0.05);毒性反应方面,3组均以骨髓抑制为主,白细胞下降及贫血发生率相近.NP组Ⅰ～Ⅱ度静脉炎(14.6%)较其他两组多,GP组Ⅲ～Ⅳ度血小板降低(16%)较其他两组严重,TP组Ⅰ～Ⅱ度外周神经毒性(38.1%)较其他两组多.结论 用于晚期NSCLC一线化疗,NP、GP、TP三种方案近期疗效相似,但毒性存在差异,故应根据患者个体情况进行选择.     

TEC方案化疗后乳腺癌患者的早期心脏毒性

目的 观察多西他赛、表柔比星、环磷酰胺(TEC)联合化疗对乳腺癌患者早期心脏毒性影响.方法 收集2009年12月～2011年6月共71例乳腺癌患者,中位年龄48 (35～64)岁,术后予6个周期TEC方案化疗,化疗前及化疗结束时、结束后12h、24 h、48 h及72 h的分别检测血清心肌肌钙蛋白Ⅰ(cTnI)及检查心电图.结果 (1)患者化疗后不同时间点cTnI出现异常的比例均较化疗前明显升高(P＜0.01); (2)共有8(11.27％)例出现心电图改变,其中窦性心动过速4例(5.63％)、ST-T改变1例(1.41％)、窦性心动过缓2例(2.82％)、房室传导阻滞1例(1.41％),除1例为Ⅱ级毒性反应外,其余7例为Ⅰ级毒性反应.结论 TEC方案化疗后可引起早期心脏毒性反应.     

聚己内酯-吐温80共聚物纳米粒在神经胶质瘤化疗中的应用

目的 研究新型载多西紫杉醇聚己内酯-吐温80共聚物(PCL-Tween 80)纳米粒在神经胶质瘤化疗中的应用.方法 以PCL-Tween 80和聚己内酯为材料,利用改良的溶剂萃取/挥发方法制备载多西紫杉醇纳米粒并进行性质表征.利用激光共聚焦显微镜观察纳米粒的细胞摄取情况,并利用噻唑蓝(MTT)法测定纳米粒对C6细胞的细胞毒作用.结果 载药纳米粒呈球形,粒径约为200 nm.PCL-Tween 80纳米粒的载药量为10%,28 d内可以释放包裹药物的34.90%.与同浓度的泰素帝(Taxotere(R))比较,载多西紫杉醇PCL-Tween 80纳米粒对C6细胞的细胞毒性作用更强.结论 载多西紫杉醇PCL-Tween 80纳米粒用于神经胶质瘤的化疗极具应用前景.