健择、顺铂方案与诺维本、异环磷酰胺、顺铂方案治疗晚期非小细胞肺癌临床对比研究

目的　观察健择 (GEM )、顺铂 (DDP)组成的GP方案和诺维本 (NVB)、异环磷酰胺 (IFO)、DDP组成的NIP方案治疗非小细胞肺癌的疗效和安全性。方法　 80例Ⅲ～Ⅳ期NSCLC患者分为两组 ,每组 40例。一组予以GP方案 :GEM 10 0 0mg/m2 ,第 1、8或 15天 ;DDP 70～ 80mg/m2 ,第 1天。另一组予以NIP方案 :NVB 2 5mg/m2 ,第 1、8天 ;IFO 1.2g/m2 ,第 1～ 4天连续给药 ;DDP 70～ 80mg/m2 ,第 1天。结果　GP组和NIP组有效率分别为 40 .0 %和 5 2 .5 % ,无统计学差异。GP组和NIP组中位生存期分别为 13 .68个月和15 .3 4个月 ,1年生存率分别为 5 4.2 9%和 5 9.46% (P >0 .0 5 )。Ⅲ～Ⅳ度白细胞减少发生率GP组和NIP组分别为 2 7.5 %和 5 5 .0 % (P <0 .0 5 )。非血液毒性反应GP组大多低于NIP组 (P <0 .0 5 )。结论　三药联合化疗方案虽然在疗效上略高于两药联合化疗方案 ,但无显著性差异 ,却增加了毒副反应。两药联合化疗方案GP是治疗晚期NSCLC患者的有效方案。而对于年纪较轻、一般情况较好的患者可予以NIP方案     

NIP方案治疗晚期非小细胞肺癌25例临床观察

目的:观察去甲长春花碱(NVB),国产异环磷酰胺(匹服平,IFO)和顺铂(DDP)联合化疗对晚期非小细胞肺癌(NSCLC)的近期疗效和毒副反应.方法:用NVB 25mg/m2静注第1、8天;IFO 2.0g静滴第1～5天,Mesna 0.4g静注于IFO用后0、4、8小时使用;DDP 30mg/m2静滴第1～3天,治疗NSCLC25例.男19例,女6例;中位年龄58岁.初治16例,复治9例;Ⅲb期10例,Ⅳ期15例.结果:部分缓解(PR)14例,总有效率56%,主要毒副反应是骨髓抑制,白细胞减少占100%,其中Ⅲ、Ⅳ度占76%,其次为静脉炎.结论:NIP方案治疗晚期NSCLC有效率高,毒性反应经G-CSF支持下可以耐受.     

长春瑞滨联合顺铂、亚叶酸钙/5-氟脲嘧啶治疗晚期食管癌

目的:观察长春瑞滨(NVB)联合亚叶酸钙(CF)、5-氟脲嘧啶(5-Fu)和顺铂(DDP)方案治疗晚期食管癌的近期疗效和毒性反应.方法:NVB 25mg/m2静脉注入,第1、8天给药;CF 200 mg静滴,第2天～6天给药;5-Fu 500mg/m2静滴6小时,第2天～6天给药;DDP 35mg/m2静滴,第2天～4天给药.28天为一个周期,完成2周期化疗后评价疗效.结果:23例晚期食管癌患者中,完全缓解2例(8.7%),部分缓解10例(43.5%),总有效率为52.2%.毒副反应主要是骨髓抑制、胃肠道反应、静脉炎.结论:NVB联合DDP、CF及5-Fu方案治疗晚期食管癌疗效较好,毒副反应可以耐受,是一个较好的联合化疗方案.     

去甲长春碱加顺铂治疗非小细胞肺癌的临床观察

目的 :观察去甲长春碱 (Navelbine ,NVB)加顺铂 (Cisplatin ,DDP)治疗非小细胞肺癌 (nonsmallcelllungcancer ,NSCLC)的疗效和安全性。方法 :治疗NSCLC 2 6例 ,采用NVB 30mg/m2 静脉推入 ,第1、8天 ;DDP 2 0mg静脉点滴 ,连用 5天。结果 :部分缓解 (PR) 10例 ,稳定 (SD) 8例 ,进展 (PD) 4例 ,总有效率 4 5 4 %。NVB的主要毒性反应为骨髓抑制 ,白细胞下降占 61 5% ,其中 3、4度占 34 6%。其他毒性反应有恶心呕吐 ( 53 9% ) ,局部静脉炎 ( 36 7% )。结论 :NVB加DDP联合治疗NSCLC有一定的疗效 ,对既往化疗无效的患者可作为挽救化疗方案使用。毒性主要为骨髓抑制 ,可用G CSF治疗     

NP与TP及GP方案治疗晚期非小细胞肺癌的近期疗效观察

目的比较长春瑞滨(vinorelbine,NVB)加顺铂(cisplatin,DDP)、紫杉醇(pacli-axe,PTX)联合DDP与吉西他滨(gemcit-abine,dFdC)加DDP分别组成的3种联合方案(NP、TP和GP)治疗晚期非小细胞肺癌(non-smallcelllungcarcinoma,NSCLC)的近期疗效和不良反应。方法NP组102例,TP组133例,GP组100例。NP组NVB25mg/m2,d1、d8;DDP70mg/m2分天给药。TP组PTX135mg/m2,d1;DDP总量90mg/m2,d2~d6。GP组dFdC1000mg/m2,30min,d1、d8;DDP总量90mg/m2,d2~d6。对临床疗效和不良反应进行对比观察。结果NP组有效率(RR)为42.16%,TP组为45.11%,GP组为47.00%。3组RR比较差异无统计学意义,P>0.05。不良反应均以骨髓抑制、脱发及恶心呕吐为主,均可耐受。GP组血小板降低较其他2组严重,P<0.05。结论NVB、dFdC或PTX联合DDP治疗晚期NSCLC具有较好的耐受性和临床疗效,不良反应可以耐受。应根据患者特点,尽可能选择个体化治疗。     

MVP方案与MIP方案治疗晚期非小细胞肺癌的疗效比较观察

目的　观察比较MVP(MMC、VDS、DDP)方案与MIP(MMC、IFO、DDP)方案治疗晚期非小细胞肺癌 (NSCLC)的疗效和安全性。方法　 44例晚期NSCLC随机分成MVP组 (每周期MMC 6mg/m2 d1,VDS 3mg/m2 ·d1·8,DDP 80mg/m2 分次于d2～ 4用 ) ,MIP组 (每周期MMC 6mg/m2 d1,IFO 1 2g/m2 +Mesna 12 0 0mgd1～ 3 DDP 80mg/m2 ,分次于d2～ 4用 ) ,二周期后评价疗效。结果　MVP组有效率为5 1 7% ,MIP组有效率为 40 % ,二组无显著差异性 (P >0 0 5 ) ,二组毒副作用MIP组较MVP组消化道反应明显 (P <0 0 5 ) ,骨髓毒性无显著差异 (P >0 0 5 )。结论　MVP方案与MIP方案是基层医院治疗晚期NSCLC高效经济的首选方案。     

NP与VIP方案治疗晚期非小细胞肺癌近期疗效观察

目的观察诺维本(NVB)与顺铂(DDP)组成的NP方案和足叶乙甙(Vp-16)与异环磷酰胺(IFO)、顺铂(DDP)组成的VIP方案对晚期非小细胞肺癌(NSCLC)的近期疗效和毒副作用.方法将经病理组织学或细胞学证实的53例晚期NSCLC患者随机分为A组(NP方案组,22例)和B组(VIP方案组,31例),分别给予NVB DDP及Vp-16 IFO DDP治疗,21 d为一周期.结果 A组有效率为50.0%,B组41.9%(P=1.43).两组剂量限制性毒性反应均为骨髓抑制,胃肠道反应和静脉炎亦常见.A组Ⅲ、Ⅳ度白细胞下降发生率为18.2%,B组45.2%(P<0.05);A组静脉炎发生率为40.9%,B组3.2%(P<0.05),但均可耐受.结论 NP方案和VIP方案治疗NSCLC疗效相近,毒性反应均可耐受.但NP方案骨髓抑制较VIP方案轻微,可作为NSCLC一线治疗方案中的首选.     

奥沙利铂联合长春瑞滨或吉西他滨治疗对顺铂和紫杉类耐药或抗拒的晚期非小细胞肺癌

目的 观察奥沙利铂(OXA)联合长春瑞滨(NVB)或吉西他滨(GEM)治疗对顺铂(DDP)和紫杉醇(PTX)或多西紫杉醇(DOC)抗拒或耐药的晚期非小细胞肺癌(NSCLC)的疗效.方法 选择对DDP和PTX或DOC抗拒或耐药的晚期NSCLC 60例,随机分为NO组(NVB + OXA)和GEMOX组(GEM + OXA),给予NVB 25mg/m2,或GEM 1 000 mg/m2,第1、8天;OXA 100mg/m2,第1天,经静脉滴入,每3周重复.结果 NO组PR 5例,SD 13例,PD 12例,总有效率(ORR)为16.7%,疾病控制率(DCR)60.0%,肿瘤进展时间(TTP) 3.3个月; GEMOX组PR 6例,SD 11例,PD 13例, ORR为20.0%,DCR 56.7%, TTP 3.4个月.两组比较差异无统计学意义(P＞0.05);两组不良反应主要是中性粒细胞减少和外周感觉神经异常,两组差异无统计学意义(P＞0.05). 结论OXA联合NVB或GEM治疗对DDP和PTX或DOC抗拒或耐药的晚期NSCLC有效.     

亚叶酸钙/氟尿嘧啶、顺铂3种方案治疗晚期胃肠道腺癌

目的 :观察两种剂量的亚叶酸钙 (CF 2 0mg/m2 ,2 0 0mg/m2 )、两种给药方法的氟尿嘧啶 (5 FU ,持续灌注和每天静滴 2小时 )与顺铂 (DDP 2 0mg/m2 )组成 3种方案分别治疗晚期胃肠道腺癌的临床疗效及不良反应。方法 :将 1999年 1月～ 2 0 0 0年 11月住院治疗的晚期胃肠道腺癌 36例患者随机分为A、B两组 ,回顾性分析 1997年 4月～ 1998年 12月住院治疗的 2 9例同种患者作为对照组C组。A组 :CF 2 0 0mg/m2 ,静滴 2小时 ,每天 1次 ,连用 5天 ;5 FU 3g/m2 ,持续静脉灌注 5天 (加入Baxter泵内 ) ,DDP 2 0mg/m2 ,静滴 2小时 ,每天 1次 ,连用 5天。B组 :CF 2 0mg/m2 ,用法同A组 ;5 FU、DDP剂量与方法同A组。C组 :CF 2 0 0mg/m2 ,用法同A、B组 ;5 FU 6 0 0mg/ (m2 ·d) ,用法同CF ;DDP方法同A、B组。以上方案每 3周为 1周期 ,连续 3个周期后评价疗效及不良反应。结果 :A组 (n =2 0 )胃癌 8例、大肠癌 12例 ,有效率 (CR +PR)分别为 5 0 %(4 / 8)、41.7%(5 / 12 ) ;B组 (n =16 )胃癌7例、大肠癌 9例 ,有效率 (CR +PR)分别为 42 .9%(3/ 7)、44 .4%(4 / 9) ;C组 (n =2 9)胃癌 14例、大肠癌 15例 ,有效率 (CR +PR)分别为 35 .7%(5 / 14)、40 %(6 / 15 )。毒副反应 :A、B两组血液毒性、胃肠道反应及肾、膀胱毒性相近     

NP与MNP方案治疗NSCLC近期疗效及毒性的对比分析

目的 :对比观察二药和三药联合化疗方案治疗非小细胞肺癌 (NSCLC)的近期疗效和毒性反应。方法 :6 2例初治的Ⅲb～Ⅳ期NSCLC ,随机分成A组 (去甲长春新碱 2 5mg/m2 静注第 1、8天 +顺铂 80mg/m2 静滴 ,分 2天 ,即NP方案 )、B组 (丝裂霉素 6mg/m2 静注第 1天 +去甲长春新碱 2 5mg/m2 静注第 1、8天 +顺铂 80mg/m2 静滴 ,分 2天 ,即MNP方案 )两组 ,分别化疗 2周期 ,每 4周为一周期。结果 :A组有效率为 33 3%、B组有效率为 37 9% (P >0 0 5 ) ;血小板降低A组为33 3% ,B组为 5 8 6 % (P <0 0 5 )。两组其余毒性反应无显著差异。结论 :二药联合可能比三药联合毒性低 ,而有效率无显著差异。     

Denosumab in patients with cancer and skeletal metastases: A systematic review and meta-analysis

Background

We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.

Methods

A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.

Results

Six controlled trials including 6142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80–0.88), delayed the onset of first on-study SRE (RR 0.83; 95% CI 0.75–0.90) and time to worsening of pain (RR 0.84; 95% CI 0.77–0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95% CI 0.90–1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95% CI 0.89–1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95% CI 0.92–2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95% CI 1.6–2.3).

Conclusions

Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events.     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

MNP和MVP方案治疗非小细胞肺癌的临床研究

目的　比较MNP和MVP方案治疗晚期非小细胞肺癌 (NSCLC)的疗效和不良反应。方法　 12 6例晚期NSCLC患者随机分为A和B组 ,A组采用MNP(丝裂霉素 去甲长春花碱 顺铂 )方案化疗。B组采用MVP(丝裂霉素 长春酰胺 顺铂 )方案化疗。至少连用 2个周期后评价疗效。结果　A组有效率为 5 4.0 % ( 3 4/63 ) ,B组有效率为 3 4.9% ( 2 2 /63 ) ,无显著性差异 (P>0 .0 5 ) ;其中对腺癌有效率A组为 44 .4% ( 16/3 6) ,B组为 3 3 .3 % ( 12 /3 6)。A组静脉炎发生率为 2 8.6% ( 14 /4 9) ,B组为 0 (P <0 .0 5 ) ,其它不良反应 2组无显著性差异。结论　MNP方案为治疗晚期NSCLC较为有效和安全的化疗方案     

The prognostic role of lymphovascular invasion and lymph node metastasis in perihilar and intrahepatic cholangiocarcinoma

IntroductionCholangiocellular carcinoma (CCA) is an aggressive malignancy with a dismal prognosis. Among curative treatment options for CCA, radical surgical resection with extrahepatic bile duct resection, hepatectomy and en-bloc lymphadenectomy are considered the mainstay of curative therapy. Here, we aimed to identify prognostic markers of clinical outcome in CCA-patients who underwent surgical resection in curative intent.Material and methodsBetween 2011 and 2016, 162 patients with CCA (perihilar CCA (pCCA): n = 91, intrahepatic CCA (iCCA): n = 71) underwent surgery in curative intent at our institution. Preoperative characteristics, perioperative data and oncological follow-up were obtained from a prospectively managed institutional database. The associations of overall- (OS) and disease-free-survival (DFS) with clinico-pathological characteristics were assessed using univariate and multivariable cox regression analyses.ResultsThe median OS and DFS were 38 and 36 months for pCCA and 25 and 13 months for iCCA, respectively. Lymphovascular invasion (LVI) and lymph node metastasis as well as surgical complications as assessed by the comprehensive complication index (CCI) and tumor grading were independently associated with OS for the pCCA (LVI; RR = 2.36, p = 0.028; CCI; RR = 1.04, p < 0.001) and iCCA cohorts (N-category; RR = 3.21, p = 0.040; tumor grading; RR = 3.75, p = 0.013; CCI, RR = 4.49, p = 0.010), respectively. No other clinical variable including R0-status and Bismuth classification was associated with OS.ConclusionMajor liver resections for CCA are feasible and safe in experienced high-volume centers. Lymph node metastasis and LVI are associated with adverse clinical outcome, supporting the role of systematic lymphadenectomy. The assessment of LVI may be useful in identifying high-risk patients for adjuvant treatment strategies.     

蛋白激酶C的下调与KBV200细胞多药耐药性的关系

目的　探讨蛋白激酶C (PKC)在肿瘤多药耐药 (MDR)中的作用。方法　3 2 P掺入法测定PKC的活性 ;Westernblot法检测KBV2 0 0细胞株PKC亚型的表达和亚细胞分布 ;实验组用十字孢碱 (SP)预孵育KBV2 0 0细胞 ;MTT法检测耐药株KBV2 0 0细胞的耐药性。结果　SP可下调膜组分和浆组分的PKC活性及总活性 ;使PKCα膜组分和浆组分的表达均降低 ,PKCβ的膜组分消失 ,浆组分PKCβ的表达稍增强 ,PKCε的膜组分和浆组分表达无变化 ;SP可降低VCR、ADR对KBV2 0 0细胞的IC50 值 (P <0 0 1)。结论　SP使KBV2 0 0细胞耐药性降低 ,可能与下调PKC有关。     

食管、贲门、胃肿瘤手术前后胆总管及胆囊内径值的对比及其意义

本文对１８０例食管、贲门、胃肿瘤手术前后ＣＢＤ及ＧＢ进行了检测和对比，发现３组病人手术后ＣＢＤ平均值均较手术前增大（Ｐ＜０．０５）。胃癌组变化明显，贲门组次之，后为食管癌组。胃癌组手术后胆囊平均值较术前增大（Ｐ＜０．０１）。结果提示：食管、贲门、胃肿瘤手术后ＣＢＤ与ＧＢ的改变可能与手术中迷走神经的损伤有关。     

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.     

GF方案与TP方案一线治疗晚期非小细胞肺癌的临床对照研究

Objective  

The aim of the study was to evaluate the efficacies of initial gemcitabine plus cisplatin (GP) and paclitaxel plus cisplatin (TP) 1st-line chemotherapies for advanced non-small cell lung cancer (NSCLC) and observe their side effects.     

肝细胞癌组织中VEGF、MMP-2和MVD的表达及其相关性研究

[目的]研究肝细胞癌(HCC)组织中血管内皮生长因子(VEGF)及基质金属蛋白酶-2(MMP-2)蛋白的表达及其临床意义,并探讨其与血管生成的关系.[方法]采用免疫组化法检测60例肝癌组织及癌旁肝组织中VEGF及MMP-2的表达,用CD34标记免疫组化法检测微血管密度(MVD).[结果]VEGF及MMP-2在癌组织中的阳性率分别为63.33%和60.00%,而在癌旁组织中的阳性率分别为33.33%和26.67%,癌组织与癌旁组织比较差异有显著性(P＜0.01).癌组织的MVD为54.92±8.55,癌旁组织的MVD为21.36±6.63,两者差异有显著性(P＜0.01).VEGF在人肝癌组织中的表达与术后复发、肝外转移、临床分期、门静脉癌栓、肿瘤直径相关.MMP-2在人肝癌组织中的表达与临床分期、门静脉癌栓、肝外转移及术后复发相关.在癌组织中MVD与VEGF及MMP-2的表达呈正相关,VEGF与MMP-2的表达亦呈正相关.[结论]HCC中VEGF及MMP-2的高表达与肿瘤血管形成有关,在HCC的发生、发展及术后复发过程中起重要作用.     

Interaction between gemcitabine and mitomycin-C in vitro

Both gemcitabine (2′,2′-difluorodeoxycytidine; dFdCyd) and mitomycin-C (MMC) are active against several solid malignancies. dFdCyd is an attractive agent for use in combination with drugs which damage DNA and with radiation therapy because of its ability to inhibit DNA replication and repair as well as its radiosensitizing effect. We hypothesized that the repair of MMC adducts in DNA might be inhibited by dFdCyd leading to a synergistic effect. To test this possibility, we studied the effect of combining dFdCyd and MMC in HT29 human colon carcinoma cells in vitro. The cells were exposed to a variety of drug concentration ratios and schedules, then assessed for clonogenic survival. D₅₀ values (drug concentration at which clonogenicity is inhibited by 50%) were calculated, and the interactive effects of the two drugs were evaluated using median effect analysis. In this approach, if the calculated combination index (CI) is <1, 1, or >1, it indicates synergism, additivity, or antagonism, respectively (Chou and Talalay 1984). We found that marked synergy (CI of 0.5–0.7) was produced by concurrent exposure to mitomycin and gemcitabine. In contrast, sequential treatment led only to additivity. These findings suggest that, when combined in an appropriate schedule, the chemosensitizing effect of gemcitabine may be beneficial in the treatment of malignancies which are sensitive to MMC. Received: 19 November 1998 / Accepted: 21 June 1999