多西紫杉醇PLGA/nHA复合微球的制备及体外释放研究

目的 制备多西紫杉醇(DTX)聚乳酸羟基乙酸(PLGA)/纳米羟基磷灰石(nHA)复合微球,研究纳米羟基磷灰石对复合微球的载药量,包封率和体外释放等性质的影响,以及抑制前列腺癌细胞的增长效应.方法 以疏水性抗癌药物多西紫杉醇作为模型药物,采用单乳化溶剂挥发法(S/O/W)制备PLGA/nHA-DTX复合微球,对载药前后的纳米羟基磷灰石进行透射电子显微镜观察和FTIR分析,并采用扫描电镜、激光粒度仪和高效液相色谱对微球的载药量、包封率、粒径及体外释药性质进行研究.结果 FTIR结果 表明纳米羟基磷灰石对多西紫杉醇有较强的吸附作用.PLGA/nHA-DTX复合微球的载药量和包封率分别为3.92%和88.7%,较之单纯的PLGA-DTX微球均有很大的提高.经过体外释放药物突释后,复合微球比单纯PLGA微球的药物释放慢.在第30 d时,复合微球和单纯的PLGA微球累积药物释率放分别为62.40%和72.70%.MTT实验结果 显示PLGA/nHA复合微球对癌细胞增长的抑制效果优于单纯PLGA微球和药物.结论 与单纯的PLGA-DTX微珠相比,由于纳米羟基磷灰石对多西紫杉醇存在较强的吸附作用,使PLGA/nHA-DTX复合微球的载药量和包封率得到了较大的提高,具有更好的药物缓释效果,抑制癌细胞增长的作用更有效.     

多西他赛联合顺泊治疗晚期非小细胞肺癌46列临床观察

目的观察多西紫杉醇联合顺铂治疗非小细胞肺癌的疗效及不良反应。方法对经细胞学或组织学证实的46例非小细胞肺癌患者给予多西紫杉醇+顺铂联合化疗。结果全组完全缓解2例,部分缓解19例,稳定18例,进展7例,总有效率为45.65%,最常见的不良反应为骨髓抑制,不良反应均可耐受。结论艾素(多西他赛)联合顺泊治疗NSCLC疗效好,不良反应可以耐受,有生存优势,值得推广应用。     

DP方案治疗晚期胃癌的临床疗效观察

目的：研究多西他赛（DTX）与顺铂（DDP）联合治疗晚期胃癌临床疗效以及毒副反应。方法：入选病例均为ⅢB/Ⅳ期胃癌,共36例,所有病人均接受两次以上的化疗周期。结果：CR3例、PR15例、SD10例、PD4例、未能评估两例、临床有效率（PR＋CR）为50%,主要副作用为胃肠道反应、白细胞减少、贫血、脱发、无治疗死亡相关病例。结论：多西他赛加顺铂方案治疗晚期胃癌疗效较好,病人耐受性良好。     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应。方法晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例。用多西紫杉醇75mg／m^2,第1天静滴,顺铂25mg／m^2。第1～3天静滴,21天为1周期,2周期后评价疗效。结果31例中CR3例,PR14例,总有效率为54．84％。主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受。结论多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受。     

Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: results from AVADO

Background

Oncologic treatment in elderly patients is challenging, due to comorbidities, often impaired organ function, limited clinical trial evidence, inadequate guidelines and no consistent ‘elderly’ definition. We report exploratory sub-analyses of safety and efficacy in elderly patients, defined as ?65 years old, in AVastin And DOcetaxel (AVADO) receiving first-line bevacizumab plus docetaxel for metastatic breast cancer (mBC).

Patients and methods

Patients with HER2-negative, locally recurrent or mBC were randomised to 3-weekly docetaxel (100 mg/m²) with placebo, bevacizumab 7.5 mg/kg or bevacizumab 15 mg/kg, for 9 cycles or until disease progression or unacceptable toxicity. Patients had no prior chemotherapy for mBC.

Results

Progression-free survival (PFS) was increased with bevacizumab in the elderly subpopulation (n = 127), the effect being greater with higher dose (hazard ratio = 0.63 [95% confidence interval (CI) 0.383–1.032] versus 0.76 [95% CI: 0.46–1.262], respectively). PFS was numerically similar in the elderly and overall populations, but the former failed to achieve statistical significance. Overall response rates for docetaxel plus placebo, bevacizumab 7.5 mg/kg and 15 mg/kg were 44.7%, 36.6% and 50.0%, respectively. Effects on survival were not statistically significant. Bevacizumab was well tolerated in elderly patients, the most common adverse effects were neutropenia and febrile neutropenia; there was no excess of grade ? 3 cardiovascular events. There was no clear correlation between baseline hypertension and its development during study treatment.

Conclusions

In this exploratory sub-analysis in AVADO, bevacizumab plus docetaxel showed efficacy in elderly patients similar to the overall study population. There were no unexpected safety signals in patients aged 65 years or older.     

6种常用抗肿瘤药物致小鼠肝损害程度的比较研究

目的:比较6种常用抗肿瘤药物的致肝损害程度。方法:取小鼠随机分为7组,每组10只,分别尾静脉注射生理盐水及临床常用剂量的顺铂(17mg·kg-1)、卡铂(67mg·kg-1)、紫杉醇(30mg·kg-1)、多西紫杉醇(17mg·kg-1)、吉西他滨(222mg·kg-1)、长春瑞滨(5.6mg·kg-1),给药第3天检测各组小鼠肝功能生化、肝组织氧化和抗氧化指标,光电镜观察肝组织病理学变化。结果:与生理盐水组比较,6个药物组给药第3天均出现肝功能生化指标与病理组织形状改变:天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、丙二醛(MDA)活性均明显升高,还原型谷胱甘肽(GSH)活性均明显降低(P<0.05或P<0.01);镜下显示细胞脂肪变性最严重的是多西紫杉醇,肝细胞坏死和瘀胆最严重的是多西紫杉醇和吉西他滨;综合各指标显示,6种药物均可致肝损害,严重程度排序为:吉西他滨≈多西紫杉醇>长春瑞滨>顺铂≈紫杉醇>卡铂。结论:6种常用抗肿瘤药物在给药第3天均出现不同程度的致肝损害,其中以吉西他滨和多西紫杉醇致肝损害较严重,建议临床使用时及早预防性应用抗氧化剂。     

多西紫杉醇、5-氟尿嘧啶联合顺铂对晚期胃癌的疗效及安全性评价

目的:评价多西紫杉醇、5-氟尿嘧啶联合顺铂对晚期胃癌的疗效及安全性。方法:58例晚期胃癌患者随机分为对照组与治疗组,每组29例。对照组给予5-氟尿嘧啶+顺铂;治疗组给予多西紫杉醇+5-氟尿嘧啶+顺铂。以21d为1个周期,治疗2个周期后评价疗效及安全性。结果:对照组总有效率为37.93%,治疗组总有效率为55.17%,2组比较差异有统计学意义(P<0.05);2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:多西紫杉醇、5-氟尿嘧啶联合顺铂治疗晚期胃癌效果显著,不增加不良反应,安全性高,值得临床推广应用。     

HPLC法测定人血浆中多西紫杉醇浓度

目的:建立测定人血浆中多西紫杉醇浓度的方法。方法:使用外标法,血浆样品经乙腈提取,振荡离心,过滤离心后进样以高效液相色谱法测定,色谱柱为KromasilC18,流动相为乙腈,流速为1.0mL·min-1,检测波长为230nm,柱温为室温,灵敏度为2.0AUFS,进样量为10μL。结果:多西紫杉醇血药浓度在0.167～3.333μg·mL-1范围内线性关系良好(r=0.9952),检测下限为0.167μg·mL-1;提取回收率在84.7%～87.5%之间,日内、日间RSD均<10%。结论:本方法简便、准确、快速,适用于多西紫杉醇血药浓度监测。     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.