吉西他滨同期放射治疗对不能手术的Ⅲ期非小细胞肺癌患者的疗效观察

背景与目的:放射治疗是肺癌的一种有效的治疗方式,加入吉西他滨后能否提高放射治疗疗效尚无定论.本研究探讨吉西他滨同期放射治疗对不能手术的Ⅲ期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效、毒副反应和生存情况.方法:共入选60例患者,分为试验组和对照组,每组各30例.试验组采用吉西他滨400 mg/m2,30 min内静滴完,每周一次,同期放射治疗,放射治疗为常规分割,DT 60～66 Gy/30～33F/6～6.5W,同时给予支持治疗.对照组除不给予吉西他滨外,其它与试验组相同.用WHO的标准评价疗效;用x2检验比较有效率、毒副反应和长期生存;用Kaplan-Meier方法计算生存率.结果:58例患者随访资料完整,随访率为96.7%.试验组和对照组的有效率分别为70.0%和60.0%(P＞0.05);消化道和血液学的毒副反应比较,差异无统计学意义(P＞0.05).Kaplan-Meier生存分析显示,试验组1、2、3年生存率分别为77.7%、58.6%、26.4%,对照组1、2、3年生存率分别为70.3%、30.1%、16.1%,经比较两者差异无统计学意义(P＞0.05).结论:对不能手术的Ⅲ期NSCLC患者,吉西他滨同期放射治疗的有效率和1、2、3年生存率均较单纯放疗有所提高,但两组比较未达统计学意义,不良反应可以耐受.     

吉西他滨固定剂量率输注联合奥沙利铂一线治疗晚期胰腺癌的Meta分析

背景与目的:有研究提示吉西他滨(Gemcitabine,GEM)固定剂量率(Fixed-dose rate,FDR)输注治疗晚期胰腺癌似有较好的疗效,Meta分析也显示含铂类联合化疗优于GEM单药化疗,本文试图通过Meta分析,探讨GEM FDR输注联合奥沙利铂(GEMOX)一线治疗晚期胰腺癌的地位和价值.方法:通过MEDLINE、EMBASE、ASCO等数据库及论文集检索国内外的相关文献.选择治疗组为GEMOX方案化疗,对照组为标准GEM单药化疗的晚期胰腺癌随机对照试验.由2位评价者分别按上述检索策略收集资料,按纳入标准入选,主要对总生存率及主要不良反应进行Meta分析.结果:从182篇文献中筛选出符合纳入标准的2个随机对照试验,共涉及869例患者.与GEM单药组比较,GEMOX组半年生存率提高9%(95%CI 0.03～0.16,P=0.005),1年生存率提高5%(95%CI-0.01～0.11,P=0.08),客观有效率提高6%(95%CI 0.02～0.10,P=0.006);WHO Ⅲ/Ⅳ度贫血发生率下降5%(95%CI-0.08～-0.01,P=0.01),恶心/呕吐提高13%(95%CI 0.08～0.18,P＜0.001),神经毒性增加14%(95%CI 0.04～0.24,P=0.009),粒细胞减少症、血小板减少症两组相似,差异无统计学意义.结论:现有的证据提示,GEM固定剂量率输注联合奥沙利铂组成的GEMOX方案一线治疗晚期胰腺癌可能有较好的应用前景,值得进行进一步的临床试验.     

不同药物膀胱灌注预防膀胱肿瘤患者术后复发的临床研究

目的 研究吡柔比星(THP)、吉西他滨(GEM)和丝裂霉素C(MMC)预防经尿道膀胱肿瘤电切术后非浸润性膀胱癌复发的临床效果和安全性.方法 将2011年1月—2013年1月收治的140例非浸润性膀胱癌患者按治疗药物分为3组,THP组50例,GEM组47例,MMC组43例.术后24 h内开始灌注,每周1次,8次后每月1次,用药至术后12个月.随访36个月观察患者的复发情况及不良反应.结果 12、24和36个月时THP组患者复发率明显低于GEM组和MMC组,且GEM组低于MMC组(P<0.05).3组总不良反应发生率比较差异无统计学意义(P>0.05).结论 THP和GEM用于预防膀胱肿瘤疗效明显高于MMC,并且无明显不良反应.     

Pancreatic carcinoma with brain metastases: case report and literature review

The case of a patient developing multiple brain metastases from carcinoma of the exocrine pancreas has been described. A 56-year-old man with stage IV pancreatic cancer attained a clinical and radiographic response while receiving the G-FLIP chemotherapy regimen (biweekly gemcitabine, irinotecan, 5-fluorouracil, leucovorin and cisplatin). After 4 months of therapy, he developed gait imbalance and weakness in the right hand. An MRI of the brain showed multiple 1-2 mm enhancing nodules in the cerebral hemispheres and pons. A subsequent biopsy confirmed that these were pancreatic carcinoma metastases. The patient experienced a rapid deterioration in his neurological status and died 3 days after brain biopsy. Previously reported cases of brain metastases from pancreatic cancer are reviewed.     

N-acetyl-l-cysteine sensitizes pancreatic cancers to gemcitabine by targeting the NFκB pathway

First-line therapy for pancreatic cancer is gemcitabine. Although tumors may initially respond to the gemcitabine treatment, soon tumor resistance develops leading to treatment failure. Previously, we demonstrated in human MIA PaCa-2 pancreatic cancer cells that N-acetyl-l-cysteine (NAC), a glutathione (GSH) precursor, prevents NFκB activation via S-glutathionylation of p65-NFκB, thereby blunting expression of survival genes. In this study, we documented the molecular sites of S-glutathionylation of p65, and we investigated whether NAC can suppress NFκB signaling and augment a therapeutic response to gemcitabine in vivo. Mass spectrometric analysis of S-glutathionylated p65-NFκB protein in vitro showed post-translational modifications of cysteines 38, 105, 120, 160 and 216 following oxidative and nitrosative stress. Circular dichroism revealed that S-glutathionylation of p65-NFκB did not change secondary structure of the protein, but increased tryptophan fluorescence revealed altered tertiary structure. Gemcitabine and NAC individually were not effective in decreasing MIA PaCa-2 tumor growth in vivo. However, combination treatment with NAC and gemcitabine decreased tumor growth by approximately 50%. NAC treatment also markedly enhanced tumor apoptosis in gemcitabine-treated mice. Compared to untreated tumors, gemcitabine treatment alone increased p65-NFκB nuclear translocation (3.7-fold) and DNA binding (2.5-fold), and these effects were blunted by NAC. In addition, NAC plus gemcitabine treatment decreased anti-apoptotic XIAP protein expression compared to gemcitabine alone. None of the treatments, however, affected extent of tumor hypoxia, as assessed by EF5 staining. Together, these results indicate that adjunct therapy with NAC prevents NFκB activation and improves gemcitabine chemotherapeutic efficacy.     

Role of human nucleoside transporters in pancreatic cancer and chemoresistance

The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5% changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade. Investigations into the mechanisms of pancreatic cancer development, progression and acquired chemoresistance have been constant for the past few decades, thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters. This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer, more specifically human equilibrative nucleoside transporter 1/2 (hENT1, hENT2), and human concentrative nucleoside transporter 1/3 (hCNT1, hCNT3), while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer. The review also discusses the incidence, current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer. Furthermore, we address the importance of chemoresistance in nucleoside analogue drugs, in particular, gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.     

低剂量吉西他滨联合奈达铂治疗晚期非小细胞肺癌疗效观察

目的：探讨低剂量持续静脉滴注吉西他滨联合奈达铂作为晚期非小细胞肺癌的疗效、不良反应、耐受性。方法：对40例晚期非小细胞肺癌患者使用低剂量吉西他滨联合奈达铂方案化疗：吉他西滨250 mg.（m^2）^-1静滴6 h,第1、8天;奈达铂80 mg.（m^2）^-1静滴,第1天,每4周为1疗程;连续使用2个疗程后评价。结果：40例总有效率（CR＋PR）为37.5%;不良反应主要为骨髓抑制（特别是血小板下降）、外周神经毒性,但恶心和呕吐较轻。结论：低剂量持续静脉滴注吉西他滨联合奈达铂是治疗晚期非小细胞肺癌可行的化疗方案之一。     

GP和TP方案治疗晚期非小细胞肺癌的随机对照临床研究

背景与目的 目前铂类药物为基础的化疗被认为是治疗晚期非小细胞肺癌（NSCI．C）的标准方案。本研究的目的是比较紫杉醇联合顺铂（TP方案）与吉西他滨联合顺铂（GP方案）治疗晚期NSCLC的近期疗效和毒性作用。方法 77例初治晚期NSCLC患者随机分为TP组和GP组，TP组39例，GP组38例。TP组：紫杉醇135mg／m^2，第1天；顺铂30mg／m^2，第1～3天。GP组：吉西他滨1000mg／m^2，第1、8天；顺铂30mg／m^2，第1～3天。化疗2～3周期后对两组的临床疗效和毒性反应进行评价。结果 TP组有效率为46．2％，GP组为42．1％，两组间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组以白细胞降低为主，均可耐受。结论 吉西他滨或紫杉醇联合顺铂治疗晚期NSCLC具有较好的耐受性和临床疗效，不良反应有所不同，但都可以耐受。     

吉西他滨联合顺铂一线治疗晚期非小细胞肺癌79例临床报告

背景和目的 化疗是晚期非小细胞肺癌治疗的主要手段,本文拟总结吉西他滨联合顺铂治疗晚期非小细胞肺癌的近期疗效、毒性反应、疾病进展时间和总生存.方法 回顾性分析我院1999年10月～2005年11月接受吉西他滨联合顺铂治疗的初治晚期非小细胞肺癌患者.79例患者中男性51例,女性28例,中位年龄53岁(21～74岁);鳞癌17例(21.5%),腺癌53例(67.1%),大细胞癌3例(3.8%),腺鳞癌1例(1.3%),未分型者5例(6.3%);分期采用AJCC 1997年标准,ⅢB期29例(36.7%),Ⅳ期50例(63.3%);行为状态(ECOG)评分0～2分,ECOG 0分15例(19.0%),ECOG 1分55例(69.6%),ECOG 2分9例(11.4%),中位ECOG评分为1分.吉西他滨800～1250 mg/m2,第1、8天静脉滴注,顺铂75～80 mg/m2,第1天静脉滴注,或30 mg/m2连用3天,静脉滴注,每三周为一周期,每例患者完成2～4周期化疗.结果 79例患者均可评价疗效,近期有效率(完全缓解 部分缓解)为31.6%,总的临床获益率(完全缓解 部分缓解 稳定)为73.4%.中位随访2.33年(0.48～6.08年),中位疾病进展时间为5.06个月,1年生存率为64.9%,2年生存率为32%.主要的毒性反应为恶心呕吐等消化道反应和血液学毒性,Ⅲ～Ⅳ度白细胞减少和血小板减少的发生率分别为25.4%和31.6%,其余的毒性反应较轻,可耐受.结论 吉西他滨联合顺铂一线治疗晚期非小细胞肺癌安全、有效,是标准方案之一.在老年患者中,疗效良好,可以推荐.对中国患者吉西他滨1000 mg/m2是可以较好耐受的剂量.