吉西他滨治疗14例晚期胰腺癌

目的：研究吉西他滨（gemcitabine)治疗晚期胰腺癌的疗效。方法：14例进行展期胰腺癌患者,用吉西他滨第1周800mg/m^2,第2周1000mg/m^2,第3周1200mg/m^2,每周1次,每次以0．9％生理盐水100ml溶解后静脉滴注,30分钟滴完,连续3周,随后休息1周为一疗程。以后每4周重复一次,共6个疗程。结果：疼痛缓解有效率为64％（9／14）,处长了中位生存期,平均为8．7个月。临床受益反应为43％。吉西他滨治疗晚期胰腺癌能显著改善晚期胰腺癌患者的临床症状,减轻疼痛。生活质量有明显提高。结论：吉西他滨可作为晚期胰腺癌综合治疗时首选的化疗药物。     

吉西他滨单药及联合用药治疗晚期胰腺癌的疗效对比:一项针对Ⅲ期随机对照临床试验的荟萃分析

背景与目的：晚期胰腺癌的治疗效果较差，生存期也较短。吉西他滨是治疗晚期胰腺癌的一线药物，有研究表明吉西他滨联合用药对患者的生存有益。本研究通过荟萃分析对比吉西他滨单药和联合用药在治疗晚期胰腺癌中的疗效。方法：检索MEDLINE、EBMreviews、EMBASE等数据库，查阅有关文献。所选Ⅲ期随机对照试验的研究对象为晚期胰腺癌，单药治疗组接受吉西他滨单药化疗，联合治疗组接受吉西他滨联合（铂类、喜树碱类，抗代谢素或靶向类）药物治疗。两名评价员独立检索资料。评价指标包括6个月、1年生存率及ORR（客观缓解率）等。结果：共检索出19篇符合要求的文章。荟萃分析结果显示联合治疗组1年生存率较单药治疗组高，两组间差异有显著性（RR：0．87，95％可信区间：[0．78，0．96]，P=0．008）。结论：吉西他滨联合用药可能有效提高晚期胰腺癌患者的生存率。     

吉西他滨固定剂量率输注一线治疗晚期胰腺癌随机对照试验的Meta分析

目的：探讨吉西他滨固定剂量率（fixed dose rate，FDR）输注一线治疗晚期胰腺癌的价值。方法：通过MEDLINE、EMBASE、ASCO和ECCO等数据库及论文集检索相关文献，选择FDR组为吉西他滨FDR化疗，对照组为吉西他滨30min化疗的晚期胰腺癌随机对照试验（randomized controlled trial，RCT）。由2位评价者依据检索策略收集资料，按纳入标准筛选文献，主要对总生存率，其次是客观缓解率和毒副反应进行Meta分析。结果：从876篇文献中筛选出符合纳入标准的2个RCT，涉及648例患者。FDR组与对照组相比，FDR组1年生存率提高6％，95％CI为0．00～0．12，P=0．060；客观缓解率提高5％，95％CI为0．00～0．09，P=0．030；3～4度中性粒细胞减少症增加25％，95％CI为0．18～0．33，P〈0．000；血小板减少症增加19％，95％CI为0．13～0．26，P〈0．000；贫血增加8％，95％CI为0．02～0．13，P=0．007；恶心呕吐增加4％，RD=0．04，95％CI为0．00～O．12，P=0．160。结论：现有证据不推荐吉西他滨FDR输注常规临床应用，但值得进一步的临床试验。     

高强度体外聚焦超声热疗治疗晚期胰腺癌近期疗效观察

目的：初步探讨高强度体外聚焦超声（high intensity focused ultrasound,HIFU)热疗治疗晚期胰腺癌的疗效及安全性。方法：13例晚期胰腺癌共接受91次（平均7次）HIFU治疗、其中4例同时应用小剂量5－FU单药化疗。结果：CR2例、PR4例，有效率46．2％；临床受益反应率（clinical benefit response,CBR)高达92．3％；中位生存期7．0个月；除1例HIFU治疗后5个月出现阻塞性黄疸外，未见其他副作用。结论：HIFU治疗晚期胰腺癌能取得一定的疗效，治疗安全性高，值得临床进一步观察研究。     

吉西他滨和顺铂联合用药治疗晚期胰腺癌患者利弊的Meta分析

目的:通过Meta分析，探讨吉西他滨和顺铂联合与吉西他滨单药治疗晚期胰腺癌的优缺点。方法:计算机检索中国知网、维普、万方数据库及中国生物医学数据库、PubMed、Sciencedirect、Embase、Cochrane Database、OVID Medline、Springer Link、EBSCO数据库，筛选观察组为吉西他滨与顺铂联合用药，对照组为吉西他滨单药治疗晚期胰腺癌的试验。检索期限为建库至2018年3月31日，同时手工查阅检索相似文献及参考文献。以上资料均由两位研究者独立进行文献筛选和资料提取，采用Review Manager 5.3软件进行Meta分析，计算结果以HR或OR值及95%置信区间（95%CI）表示。结果:共纳入文献12篇，包括观察组850例和对照组753例。Meta分析结果显示:疗效方面，总生存期、1年生存率及半年生存率方面吉西他滨和顺铂联合用药与吉西他滨单独用药无明显区别［HR总生存期=0.97，95%CI为（0.83，1.12）,P=0.65＞0.05；OR1年生存率=1.02，95%CI为（0.76，1.38），P=0.89＞0.05；OR半年生存率=1.12，95%CI为（0.77，1.64），P=0.56＞0.05］；而客观缓解率（ORR）则具有边缘性统计意义［OR客观缓解率=1.54，95%CI为（1.00，2.37），P=0.05］；毒副反应方面，吉西他滨和顺铂联合用药的毒副作用明显高于吉西他滨单独用药［OR3/4度中性粒细胞减少=1.70，95%CI为（1.27，2.27），P=0.000 4＜0.05；OR3/4度血小板减少=1.96，95%CI为（1.55，2.49），P＜0.000 01；OR胃肠道毒副作用=2.98，95%CI为（1.95，4.55），P＜0.000 01］。结论:吉西他滨联合顺铂治疗晚期胰腺癌虽然在ORR中能使患者受益，但不能使患者获得比单用吉西他滨更好的临床疗效及远期预后，反而使中性粒细胞减少、血小板减少及胃肠道反应等毒副反应加剧。因此，临床上不应提倡吉西他滨联合顺铂用药作为一线临床用药，应选用更加合理有效的化疗用药方案。     

晚期胰腺癌全身化疗的疗效观察

背景与目的:晚期胰腺癌是恶性程度很高的肿瘤,全身化疗是其主要的治疗方法。本研究拟观察、比较三种不同化疗方案对晚期胰腺癌的客观疗效及其临床受益反应。方法:对我科2000年2月～2001年4月期间收治的经病理检查证实的74例晚期胰腺癌患者的临床资料进行回顾性分析,其中26例采用5-氟尿嘧啶、醛氢叶酸、顺铂方案治疗(A组);23例采用吉西他滨单药治疗(B组);25例采用吉西他滨联合5-氟尿嘧啶、醛氢叶酸方案治疗(C组)。采用Kaplan-Meier法分析患者生存期,Cox比例风险回归模型分析影响预后的因素。结果:A、B、C三组客观缓解率分别为7.7%、17.4%与24.0%,三组间无显著性差异(P=0.261,χ2检验);临床受益反应率分别为19.2%、47.8%与60.0%,B、C组优于A组,差异具有显著性(P<0.05,χ2检验)。A、B、C三组中位生存期分别为6.50个月(95%CI=5.00,7.99)、8.03个月(95%CI=6.72,9.35)、8.79个月(95%CI=7.31,10.26),B、C组长于A组,差异有显著性(Breslow=8.85,P=0.0119)。三组间血液学毒性和非血液学毒性发生率差异无显著性。结论:吉西他滨与5-氟尿嘧啶、醛氢叶酸联合作为一线方案治疗晚期胰腺癌有一定的客观缓解率,可改善患者的生活质量,患者耐受良好,值得进一步研究。     

吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效比较

目的：比较吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效。方法：前瞻性分析了2002年3月-2005年8月收治的56例局部晚期胰腺癌患者的疗效，其中26例采用吉西他滨联合适形放疗（放化组），30例采用吉西他滨联合顺铂（化疗组）。结果：可评估病例54例，放化组有效率（CR＋PR）为68．O％，化疗组有效率（CR＋PR）为37．9％，两组差异有统计学意义（P=0．0275）。放化组和化疗组的6月生存率分别为84．O％和62．1％（P=0．0728）；12月生存率分别为64．O％和37．9％（P=0．0561）。两组差异无统计学意义。放化组和化疗组的临床获益率（CBR）分别为84．0％和69．0％，两者差异无统计学意义（P=0．1976）。放化组和化疗组的严重不良事件总发生率分别为36．0％和44．8％，无统计学差异（P=0．5103）。结论：在近期疗效方面，吉西他滨联合适形放疗的近期疗效优于吉西他滨联合顺铂；而远期生存率，吉西他滨联合适形放疗虽然显示出一定的优势，但无统计学意义，二者在CBR和严重不良事件发生率无明显差异。     

吉西他滨联合高强度聚焦超声治疗中晚期胰腺癌的临床观察

目的:探讨吉西他滨联合高强度聚焦超声(HIFU)治疗中晚期胰腺癌的疗效和安全性.方法:64例中晚期胰腺癌患者随机分为两组,A组:高强度聚焦超声治疗;B组:吉西他滨联合高强度聚焦超声治疗,比较两组的疗效、临床受益率和不良反应.结果:A组有效率43.8%、B组75.0%(P＜0.05),A组临床受益率56.3%,B组84.4%(P＜0.05);B组6个月、12个月生存率分别高于A组;两组不良反应差异无统计学意义(P＞0.05).结论:吉西他滨联合高强聚焦超声治疗中晚期胰腺癌具有更好的疗效.     

吉西他滨为基础的化疗方案治疗进展期胰腺癌的临床研究

背景与目的:进展期胰腺癌预后差.吉西他滨可以改善胰腺癌患者的生存质量,但吉西他滨联合方案疗效是否优于单药,还存在争议,国内更缺乏相关的临床研究.本研究目的是比较吉西他滨为基础的联合化疗方案与吉西他滨单药治疗进展期胰腺癌的疗效.方法:回顾性分析2000～2005年收治的40例经临床或病理确诊的进展期胰腺癌临床资料,其中吉西他滨单药组15例,吉西他滨剂量为1 000 mg/m2,每周1次,连用7周,休息2周,之后每周1次,连用3周,4周重复;吉西他滨联合治疗组25例,联合化疗方案包括吉西他滨1 000 mg/m2,每周1次,连用2周,分别联合:(1)氟尿嘧啶425～600 mg/m2,静脉滴注或持续静脉泵入,d1-5,3周重复;(2)顺铂60～75 mg/m2,分第1、2天,3周重复;(3)奥沙利铂85～130 mg/m2,d1,3周重复;(4)卡培他滨l000 mg/m2,2次/天,d1-14,3周重复.采用Kaplan-Meier生存曲线分析患者的生存期,并比较两组间的临床受益反应、中位疾病进展时间、中位生存时间和不良反应.结果:吉西他滨联合组与单药组患者的临床受益反应均得到改善(56.0% vs.46.7%),但疾病控制率、中位生存时间、临床受益反应在两组之间差异无统计学意义(P＞0.05),不良反应的发生率也相似(P＞0.05).对Ⅲ～Ⅳ期患者进行分层分析,发现吉西他滨联合组疾病控制率高于单药组(75.0% vs.45.5%),但无统计学意义(P=0.13).结论:吉西他滨联合方案与单药治疗进展期胰腺癌相比,疗效、临床受益反应、中位生存时间两组相似.     

吉西他滨联合奥沙利铂治疗晚期胰腺癌疗效观察

目的：观察GEMOX联合方案治疗晚期胰腺癌的疗效和毒副反应。方法：19例确诊晚期胰腺癌患者接受至少2个周期的GEMOX联合方案化疗，吉西他滨1000mg／m^2，静脉滴入，d1、d8；奥沙利铂130mg／m^2，静脉滴入，d1。每21d重复。结果：1例CR，5例PR，8例SD，5例PD，总有效率为31．6％(6／19)，毒副反应可以耐受，没有化疗相关的死亡。结论：吉西他滨加奥沙利铂联合化疗是治疗晚期胰腺癌安全有效的方案，可以使部分患者得到临床受益。但需要有Ⅲ期的随机临床试验与吉西他滨单药化疗进行比较，以明确此联合方案的优势。     

Retrospective analysis of high intensity focused ultrasound combined with S-1 in the treatment of metastatic pancreatic cancer after failure of gemcitabine

The purpose of this study was to verify the efficacy and safety of high intensity focused ultrasound therapy (HIFU) combined with S-1 in the treatment of metastatic pancreatic cancer after failure of gemcitabine (GEM). In total, 120 patients with GEM-refractory PC who received HIFU and S-1 between Aug 2012 and December 2014 were randomly assigned to 2 groups. The patients in group A (n = 61) received HIFU in combination with S-1 and those in group B (n = 59) were given S-1 alone. S-1 was administered orally twice a day on days 1-14. Cycles were repeated every 21 days. The follow up time was 3~19 months in both groups. The median overall survival (OS) time and progression free survival (PFS) were analysed by Kaplan-Meier method and Logrank test. The pain remission rate of the two groups was compared by χ² test. Patient characteristics and prognostic factors were compared. Patient characteristics did not significantly differ between the 2 groups. Median OS was significantly longer in group A (10.3 months) than in group B (6.6 months, P = 0.000). Median PFS was also significantly longer in group A than in group B (5.1 months vs 2.3 months, P = 0.000). Meanwhile, the pain remission rate was markedly higher in group A than in group B (57% vs. 20%, P = 0.000). There were mild side effects and no significant difference was observed between the two groups. The treatment effect was independently associated with a good outcome. HIFU in combination with S-1 might be effective and well tolerated as salvage chemotherapy in the treatment for metastatic pancreatic cancer.     

Combination chemotherapy with gemcitabine and S-1 for advanced pancreatic cancer

The incidence and mortality of pancreatic cancer has increased very rapidly in Japan. The five-year survival rate is still poor at less than 10%, because it is commonly considered to be linked to a high incidence of distant metastasis even at the initial diagnosis as well as to the tumor's resistance to anticancer agents. Although gemcitabine has been the most widely used chemotherapeutic agent in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has obvious limitations. Therefore, various combinations with other agents have been investigated to improving the survival of patients with APC. Under these circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral fluorouracil derivative, to determine the maximum tolerated dose and to evaluate the activity and toxicity of such a combination in patients with APC. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1 30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the recommended dose. The toxicities observed were mainly hematological ones with mild non-hematological toxicities. An encouragingly high response rate was observed. This result is very promising, but the survival benefit in comparison with gemcitabine monotherapy needs to be confirmed in a future randomized clinical trial.     

胰腺癌高强度聚焦超声治疗对全身炎症反应的影响

目的:分析胰腺癌患者高强度聚焦超声（HIFU）治疗后全身炎症反应的情况。方法:筛选符合入组条件的患者34例,根据是否在HIFU治疗前2周内行化疗分为化疗组与未化疗组。统计患者HIFU治疗前后外周静脉血中白细胞（WBC）、中性粒细胞（NE）、淋巴细胞（LY）、C反应蛋白（CRP）及肿瘤坏死因子-α（TNF-α）数值;利用SPSS 20.0统计软件分析各项指标变化;Kaplan-Meier法绘制生存曲线;Cox回归法分析影响生存时间的独立预后因素。结果:34例患者外周静脉血中WBC、NE和TNF-α在HIFU 治疗前后的差异无统计学意义（P=0.146、P=0.053、 P=0.628）,LY和CRP在HIFU治疗前后差异显著（P=0.002、P=0.002）;多因素Cox回归分析结果示WBC、NE、LY、CRP和TNF-α各指标变化不是HIFU治疗后生存时间的独立预后因素（P=0.169、P=0.757、P=0.884、P=0.161、P=0.950）;分层分析显示,化疗组（P=0.038）及未化疗组（P=0.039）CRP在HIFU 治疗前后均有统计学差异,但治疗前后CRP的差值在化疗与未化疗组间并无差异（P=0.97）。结论:胰腺癌HIFU治疗会导致体内轻度炎症反应,不影响患者生存时间,是否行化疗对HIFU相关炎症反应无显著影响。     

Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer

BACKGROUND: In this non-randomized study we aimed to assess the efficacy of the addition of low molecular weight heparin (LMWH) to gemcitabine (GEM) plus cisplatinum (CDDP) combination chemotherapy on survival by prevention of thromboembolic complications in patients with advanced pancreatic cancer (APC). PATIENTS AND METHODS: Between November 1999 and February 2004, 69 consecutive patients with APC were treated with GEM (800 mg/m2, day 1, day 8) plus CDDP (35 mg/m2, day 1, day 8) every 21 days +/-LMWH (nadroparine calcium, 2,850 IU/day until disease progression). Ten out of 35 patients in LMWH group and 10 out of 34 patients in chemotherapy alone group had primary inoperable locally advanced disease and the rest of the patients had metastatic disease. RESULTS: Total response rate was 58.8% (11.7% CR) for the patients treated with LMWH and 12.1% for those treated without LMWH (P = 0.0001). LMWH group had a better median time to progression (TTP) and survival when compared to control group (7.3 vs. 4.0 months, P = 0.0001; 13.0 vs. 5.5 months, P = 0.0001). The toxicity was similar and acceptable in both groups. CONCLUSION: Addition of LMWH to GEM plus CDDP combination significantly improved the response and survival in patients with APC and the current schedule deserves to be tested in phase III trials.     

吉西他滨联合替吉奥胶囊治疗晚期胰腺癌的疗效观察

目的探讨吉西他滨联合替吉奥胶囊化疗方案与吉西他滨单药治疗进展期胰腺癌的疗效。方法对2008年1月至2011年1月收治的52例晚期胰腺癌患者的临床资料进行回顾性分析,其中28例采用吉西他滨联合替吉奥胶囊方案治疗(A组);24例采用吉西他滨单药治疗(B组)。采用Kaplan-Meier法分析患者的生存时间,并比较两组患者的客观缓解率、临床受益反应(CBR)、中位疾病进展时间、中位生存时间和不良反应。结果 A组有效率明显高于B组(32.1%vs.20.8%),差异有统计学意义(P=0.039)。A组疾病控制率(DCR)高于B组(67.9%vs.45.8%),但差异无统计学意义(P=0.230)。A组患者CBR缓解率高于B组(72.1%vs.46.9%),差异无统计学意义(P=0.41)。A组的中位生存时间为10.2个月(95%CI:8.0～11.8个月),高于B组的8.03个月(95%CI:3.8～10.9个月),差异有统计学意义(P=0.045);A、B两组的中位疾病进展时间分别为3.6个月和3.0个月(P=0.721)。A组的6个月生存率(72.7%)略高于B组(66.8%),但差异无统计学意义(P>0.05)。两组不良反应的发生率也相似(P>0.05)。结论吉西他滨联合替吉奥胶囊治疗方案与单药治疗晚期胰腺癌相比,在客观疗效、中位生存时间表现出一定优势,疾病控制率及临床受益反应也有所提高,且不良反应可耐受,是晚期胰腺癌的有效治疗方案。     

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.     

An Updated Meta-analysis and System Review:is emcitabine+Fluoropyrimidine in Combination a Better herapy Versus Gemcitabine Alone for Advanced and Unresectable Pancreatic Cancer?

Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabinechemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstlinechemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide.Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic reviewand a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidinecombination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabinetreatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigatethe efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locallyadvanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials.Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited.The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For theprimary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantlybetter outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression freesurvival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients)(HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we foundthat in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12);while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95).Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associatedwith more toxicity compared with gemcitabine monotherapy.     

单药口服替吉奥与单药吉西他滨对中晚期胰腺癌的综合疗效比较

目的 探究单药口服替吉奥与单药吉西他滨对中晚期胰腺癌的综合疗效.方法 选取中晚期胰腺癌患者92例为研究对象,针对患者的临床资料进行了回顾性的比较研究.结果 (1)替吉奥组46例患者中,完全缓解4例,部分缓解10例,稳定16例,进展16例,有效率为30.4%;吉西他滨组46例患者中,完全缓解4例,部分缓解9例,稳定15例,进展18例,有效率为28.3%.2组临床治疗有效率组间比较,差异均无统计学意义;(2)替吉奥组46例患者6个月生存患者22例,1年的生存患者16例,2年生存患者4例;吉西他滨组46例患者6个月生存患者23例,1年的生存患者15例,2年生存患者3例.2组不同时点的生存率水平相当,组间差异无统计学意义;(3)2组患者化疗前后CEA和CA-199水平差异不大,且组间差异无统计学意义;(4)2组不良反应发生率无显著差异.结论 单药口服替吉奥与单药吉西他滨对中晚期胰腺癌的综合疗效相当,近远期综合治疗效果差异不明显.