洛铂联合吉西他滨治疗晚期胰腺癌临床观察

目的观察洛铂联合吉西他滨治疗晚期胰腺癌的t临床疗效及不良反应。方法30例晚期胰腺癌患者随机分为两组,观察组18例,给予GP方案（洛铂联合吉西他滨）,21d为1个周期;对照组12例,给予GEMOX方案（奥沙利铂联合吉西他滨）,21d为1个周期,均至少化疗2个周期。结果30例患者均可评价疗效和不良反应。观察组临床受益反应率明显优于对照组（53％vs32％,P〈0．05）;观察组中位生存期和1年生存率也明显优于对照组（P〈0．05）;主要不良反应（血小板减少、胃肠道反应、末梢神经炎）较对照组轻,其他不良反应两组相似,患者均可耐受。结论洛铂联合吉西他滨治疗晚期胰腺癌近期临床疗效较高,不良反应可以耐受。     

吉西他滨联合厄洛替尼治疗晚期胰腺癌12例临床观察

目的观察吉西他滨联合厄洛替尼治疗晚期或进展期胰腺癌的临床疗效、获益反应和不良反应。方法回顾性分析12例接受吉西他滨联合厄洛替尼治疗的局部晚期或转移性胰腺癌患者的临床资料。所有患者均接受至少两个周期吉西他滨联合厄洛替尼的治疗。吉西他滨于第1天和第8天800-1 000 mg/m^2静脉滴注,每21 d为一个周期;厄洛替尼口服150 mg/d。治疗两个周期后复查CT评价疗效。结果 1例因腹泻严重退出。11例患者中无达到完全缓解者,1例（9.09%）获得部分缓解,6例（54.5%）病情稳定,4例（36.4%）病情进展,疾病控制率为63.6%,临床获益率为72.7%,中位无进展生存期为4.5个月,中位生存期8.4个月。血液学毒性发生率为75.0%,其中Ⅲ-Ⅳ度白细胞下降的发生率为25.0%,Ⅲ-Ⅳ度血小板下降发生率为8.3%。皮疹发生率为41.7%,均为Ⅰ-Ⅱ度,1例出现Ⅲ度腹泻退出,4例出现Ⅰ度转氨酶升高。无化疗相关的死亡。结论吉西他滨联合厄洛替尼治疗晚期胰腺癌,可以延长生存时间,提高生活质量,总体临床耐受性好。     

两种不同含铂类方案治疗晚期非小细胞肺癌随机对照研究

目的：评价吉西他滨联合顺铂（GP方案）与紫杉醇联合顺铂（TP方案）治疗晚期非小细胞肺癌（NSCLC）的疗效和毒性反应。方法：79例患者随机分为GP组和TP组,GP组：吉西他滨1 000 mg/m^2,30min,d1、d8;顺铂30 mg/m^2,d1~d3;TP组：紫杉醇135 mg/m^2,d1;DDP 30 mg/m^2d1－d3;对两组的临床疗效和毒性反应进行对比观察。结果：GP组有效率（RR）为41.0%,中位生存期（MST）10.9个月,中位疾病进展时间（TTP）4.5个月;TP组RR为42.5%,MST 10.5个月,TTP 4.3个月;两组比较差异无统计学意义（P〉0.05）,GP组不良反应以血小板降低为主,TP组以乏力和外周神经毒性为主,均可耐受。结论：吉西他滨或紫杉醇联合DDP治疗晚期NSCLC具有较好的耐受性和临床疗效,二者疗效和生存率比较没有显著性差异,不良反应有所不同但都可以耐受,应根据患者特点,尽可能选择个体化治疗。     

吉西他滨对胰腺癌细胞株PANC-1中TMS1/ASC基因表达及启动子甲基化的影响

目的:观察吉西他滨(GEM)对胰腺癌细胞株PANC-1中甲基化诱导静止基因(TMS1/ASC)的表达及其启动子区甲基化的影响,并讨论其疗效机制。方法:将对数生长期PANC-1分为两组,以加入4.27μg/ml的GEM作用于PANC-1细胞者为实验组(GEM组),以不加GEM者为对照组,分别继续培养24h,采用DNA原位末端标记(TUNEL)法结合激光共聚焦显微镜观察两组PANC-1细胞凋亡和细胞核形态变化;采用RT-PCR检测两组PANC-1细胞中TMS1/ASC mRNA的表达情况;采用重亚硫酸盐限制内切酶法(COBRA)检测两组PANC-1细胞中TMS1/ASC的甲基化状态。结果:(1)GEM组中PANC-1凋亡明显(FITC和PI双染阳性),对照组未见PANC-1凋亡;(2)GEM组PANC-1的TMS1/ASC mRNA表达显著高于对照组(P<0.01);(3)GEM组PANC-1中TMS1/ASC启动子区甲基化率显著低于对照组(P<0.01)。结论:GEM可能通过促进PANC-1细胞凋亡,上调TMS1/ASC mRNA表达以及抑制TMS1/ASC启动子区的甲基化而起到治疗胰腺癌的作用。     

Preoperative chemoradiation followed by surgical resection for resectable pancreatic cancer: a review of current results

Background

There has been an interest in the interdisciplinary and multimodality approach that combines chemotherapy and radiation therapy as a preoperative treatment for patients with resectable pancreatic cancer.

Methods

Literature search of databases (Medline and PubMed) to identify published studies of preoperative chemoradiation for resectable pancreatic cancer (potentially resectable and borderline resectable) was undertaken. Response to treatment and survival outcomes was examined as endpoints of this review.

Results

Seventeen studies; eight phase II studies, and nine observational studies, comprising of 977 patients were reviewed. Gemcitabine-based chemotherapy with radiotherapy was the most common preoperative regimen. Following preoperative treatment, pancreatic surgical resection was performed in 35–100% (median = 61%) of patients after a range of 6–32 weeks (median = 7 weeks). Rate of pathological response was complete in 5–15% of patients, partial in 33–60% and minimal in 38–42%. The median overall survival ranged from 12 months to 40 months (median = 25 months) with a 5-year overall survival rate ranging between 8% and 36% (median = 28%). Patients who underwent chemoradiation but did not undergo surgery survived a median period of 7–11 months (median = 9 months).

Conclusion

Preoperative gemcitabine-based chemoradiation followed by restaging and surgical evaluation for pancreatic resection may identify a sub-population of patients with resectable disease who would benefit the most from surgery. Investigation of this schema of preoperative therapy in a randomized setting of resectable pancreatic cancer is warranted.     

吉西他滨联合奈达铂同期放化疗治疗局部晚期鼻咽癌的疗效观察

目的评价吉西他滨加奈达铂(GN组)和氟尿嘧啶加顺铂(PF组)同期放化疗治疗Ⅲ、Ⅳa期鼻咽癌的疗效,毒副作用和生存率。方法经病理确诊的Ⅲ、Ⅳa期鼻咽癌120例随机分为2组,GN组(治疗组)60例,PF组(对照组)60例。吉西他滨800 mg/m2,d1,d8;奈达铂70 mg/m2,d1;氟尿嘧啶500 mg/m2,d1～d5;顺铂80 mg/m2,d1,均是静脉滴入,在放疗第1,5周给予,一共2周期。结果 GN组同期放化疗的有效率为100%,PF组96.7%。3年生存率分别为GN组81.7%,PF组78.3%,消化道反应发生率分别为GN组53.3%,PF组76.7%。结论同期GN化放组和PF化放组的近期疗效和3年生存率相近。GN化放组的不良反应较轻,患者耐受好。     

吉西他滨联合多西紫杉醇新辅助化疗方案在晚期非小细胞肺癌中的应用观察

目的探讨吉西他滨联合多西紫杉醇新辅助化疗方案在晚期非小细胞肺癌中的应用观察。方法 2008年2月至2010年10月符合入选标准晚期非小细胞肺癌患者134例分为GT组64例,NP组70例,观察两组病例临床疗效、分期下调率及毒性反应。结果 GT组总有效率46.87%,NP组总有效率51.42%,两组比较,差异无统计学意义(P>0.05)。两组不良反应中白细胞减少、血小板减少、发生率进行比较,差异无统计学意义(P>0.05)。两组病例消化系统不良反应恶心呕吐症状进行比较,差异有统计学意义(P<0.05)。结论吉西他滨联合多西紫杉醇新辅助化疗方案与含铂方案相比近期疗效,总有效率相似,胃肠道反应轻微易于被患者所接受。     

Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers

Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade. New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs. Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival, although the effect was minimal. Little or no improvement in survival with recent molecular-targeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer. Recently, the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time. For biliary tract cancer, gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy. Further improvement in survival is expected by the addition of cetuximab.     

多西他赛和吉西他滨分别联合顺铂治疗晚期非小细胞肺癌效果比较

目的 比较多西他赛与吉西他滨联合顺铂方案治疗晚期非小细胞肺癌(NSCLC)的临床疗效及不良反应.方法 120例晚期非小细胞肺癌患者完全随机分为2组.多西他赛组60例给予多西他赛37.5 mg/m2,第1、8天;顺铂25 mg/m2,第1～3天.吉西他滨组60例给予吉西他滨1000 mg/m2,第1、8天;顾铂用量同前.化疗每3周重复,每周期评价不良反应,评价疗效并随访生存期.结果 20例患者均可评价疗效和不良反应,2组有效率分别为多西他赛组45.0%(27/60)和吉西他滨组43.3%(26/60),1年生存率分别为45%和43.3%,两组之间有效率和1年生存率均无统计学意义(P＞0.05).不良反应主要为骨髓抑制和肝功能损害[多西他赛组白细胞产减少率为85.0%(51/60),吉西他滨组为78.0%(47/60),2组差异无统计学意义(P＞0.05);2组肝功能损害率分别为33.3%(20/60)、26.7%(16/60),差异有统计学意义(P＜0.05)].结论 多西他赛与吉西他滨联合顺铂方案治疗晚期NSCLC均具有较好的疗效,且两者的疗效相似,不良反应可以耐受,可以作为临床一线治疗.

Abstract：

Objective To compare the efficacy and safety of docetaxel plus cisplatin and gemcitabine plus cisplatin in advanced non-small cell lung cancer (NSCLC). Methods A total of 120 patients with advanced NSCLC were divided into two groups. The patients received docetaxel in docetaxel group. In gemcitabine group the patients received gemcitabine and cisplatin. The treatment schedule was repeated every 3 weeks. The toxicity,quality response and survival rate of life were evaluated after every cycle. Results The response rates of the docetaxel group and the gemcitabine group were 45% and 43.3%,respectively. One-year survival rates in the two groups were 45% and 43.3%,respectively. The response rate,one-year survival time showed no significance (P ＞0.05). The main side effects were myelosupp ression,nausea and vomiting. Conclusion Regimens of DC and GC are both safe and effective in the treatment of advanced stage NSCLC. They can be used as the first regimen of chemotherapy in patients with advanced stage NSCLC.     

miRNA profiling in pancreatic cancer and restoration of chemosensitivity

Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. The present study identifies a series of miRNAs which were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues. Gemcitabine resistant MIA PaCa-2 cells possessed distinct ALDH-positive CSC fraction expressing stem cell markers OCT3/4 and CD44 and chemoresistance marker class III β-tubulin (TUBB3) which decreases on transfection with miR-205 resulting in the restoration of chemosensitivity to gemcitabine.