肺癌患者雾化吸入氟脲嘧啶后血清及组织药物浓度测定

目的 观察肺癌患者雾化吸入氟脲嘧啶（５－ＦＵ）后血清及呼吸系统组织中药物的分布。方法 １０例肺癌患者给予１．２５％５－ＦＵ４０ｍｌ雾化吸入,每日２次,同期１０例条件相同的肺副产品徐 给予５－ＦＵ０．７５ｇ静脉滴注,每日１次。用高压液相色谱法测定患者用药后血清及呼吸系统组织中５－ＦＵ浓度。结果 雾化给药组５－ＦＵ最高血清浓度为（４．５９±１．７７）ｍｇ／Ｌ,静脉组为（１０．４６±１．４６）ｍｇ／Ｌ。     

氟尿嘧啶雾化吸入治疗晚期肺癌17例

氟尿嘧啶雾化吸入治疗晚期肺癌１７例贺洪源冯健（上海友谊医院，上海２０００５２）静脉给药、动脉介入和口服是化疗药物常用的治疗途径。而通过雾化吸入化疗药物治疗肺癌，国内尚未见报道。我院自１９９４年１０月至１９９６年９月，采用氟尿嘧啶（５－ＦＵ）雾化吸入治...     

肺癌吸入化疗深入研究

雾化吸入这一新的化疗方法,对肿瘤发挥最大杀细胞作用,治疗肺癌很有效,对其他器官无毒副作用。经口腔向支气管系统吸入抗癌药气雾微粒。 实验研究用蒙古犬。用新型高敏液相层析仪(HPLC)检测组织和血中5-Fu及其代射产物FUR和FUdR。全麻及呼吸机密闭循环式通气条件下,用超声雾化器吸入5-Fu(50mg/kg)和必消痰的混合气雾。     

三氧化二砷超声雾化吸入治疗肺癌的临床观察

目的观察三氧化二砷(As2O3)超声雾化吸入配合全身化疗治疗肺癌的临床疗效.方法 60例肺癌患者随机分为两组,对照组30例,采用MVP方案,21 d为一周期,2～3周期为一疗程;试验组30例,在同对照组用药的基础上,将As2O3液加入超声雾化吸入器中吸入,每次药物配比为:生理盐水50 ml As2O3 2 mg α-糜蛋白酶5 mg,每日3次,每两次间隔4 h,共吸入砷总量6 mg/d,28 d为一疗程.结果加用As2O3超声雾化吸入组治疗有效率明显高于单纯化疗组.试验组PR率为46.7%,对照组为20.0%(χ2=4.8,P＜0.05);试验组PD率为6.7%,对照组为26.7%(χ2=4.3,P＜0.05).结论三氧化二砷超声雾化吸入可以提高肺癌的治疗有效率,与化疗有协同作用,至少可以作为非手术适应证和一般身体状况不能耐受放疗或化疗耐药患者的一种辅助治疗备选方案.     

高频加氧雾化吸入顺铂法治疗肺癌的临床及药代动力学研究

目的：探讨高频加氧雾化吸入顺铂对肺癌的治疗效果及药代动力学特点。方法：以高频呼吸机联动超声雾化器雾化顺铂经口吸入的方法治疗肿癌并进行临床及实验药代动力学研究。结果：６８例肺癌中ＣＲ（完全缓解）４例（５．９％）、ＰＲ（部分缓解）４３例（６３．２％）,ＲＲ（缓解率）６９．１％,另有气管癌１例疗效达ＰＲ,袖式肺切除吻合口癌残留２例均达ＣＲ。全组７１例ＲＲ７０．４％（５０／７１）,药代动力学：（１）临床部     

5-FU超声雾化吸入联合放化疗治疗非小细胞肺癌的临床研究

探讨 5 FU超声雾化吸入联合放疗及全身化疗治疗非小细胞肺癌 (NSCLC)的疗效 ,探讨一种新的非手术综合治疗方案。60例非小细胞肺癌患者随机分为两个组。研究组采用 5 FU超声雾化吸入联合常规放疗及以顺铂为主的全身化疗 2个周期 ,对照组采用常规放疗及全身化疗。结果示研究组和对照组的总有效率分别为 86 67%(2 6/3 0 )和 63 3 3 % (19/3 0 ) ,χ2 =4 3 5 6,P <0 0 5。 1、2、3年生存率研究组为 79 89%、5 6 2 6%和 3 0 3 9% ;对照组分别为 5 1 5 7%、3 4 81%和 11 60 % ,χ2 =4 42 1,P <0 0 5。两组的毒副反应差别无统计学意义 ,P >0 0 5。 5 FU超声雾化吸入联合放疗和以顺铂为主的全身化疗提高了NSCLC的 1、2、3年生存率 ,毒副反应可耐受 ,是一种有效的非手术综合治疗方案。     

雾化吸入化疗药治疗晚期肺癌的近期疗效观察

自 1995年 12月至 1999年 12月 ,我们采用超声雾化吸入 5 氟脲嘧啶 (5 ＦＵ)的方法治疗晚期肺癌 39例 ,近期疗效较对照组明显升高 ,现报告如下。1　资料与方法1.1　病例与分组　所有患者均经细胞学或病理学确诊 ,Ｋａｒｎｏｆｓｋｙ评分在 6 0分以下 ,平均年龄 6 9.7岁。患者入院前未接受任何治疗 ,且不适宜手术及化放疗。将患者随机分成观察组和对照组。观察组 39例 ,男性2 7例 ,女性 12例 ;周围型 13例 ,中心型 2 6例 ;ⅢＡ期13例 ,ⅢＢ期 2 4例 ,Ⅳ期 2例。对照组 2 1例 ,男性 13例 ,女性 8例 ;周围型 8例 ,中心型 13例 ;ⅢＡ期 7例 ,Ⅲ…     

老年肺癌患者术后辅助化疗临床意义回顾性分析

目的:了解含铂方案术后辅助化疗对老年非小细胞肺癌患者生存期的影响.方法:回顾性分析2001-01-2004-12上海户籍≥65岁的老年非小细胞肺癌手术患者314例.分为年轻老年人(65～＜70岁)、中等老年人(70～＜75岁)、高龄老年人(≥75岁)3组.结果:术后愿意接受辅助化疗的患者仅29.9%.接受辅助化疗与未接受化疗者相比,未明显延长生存期(P=0.636 5),中位生存期分别为(39.4±8.39)和(25.70±6.83)个月.其中61.7%患者能完成3/4个周期,完成≥3个周期者比未能完成者有显著的生存获益(P=0.033 6),中位生存期分别为(86.60±26.99)和(23.40±6.01)个月,降低死亡风险(P=0.002,HR=0.806).经Cox多因素分析,年龄不是影响生存的主要因素,而病理分期及含铂方案术后辅助化疗(≥3个周期)是影响生存的主要因素.结论:老年非小细胞肺癌患者术后能接受≥3个周期化疗者可明显延长生存期,降低死亡风险.高龄患者对含铂方案辅助化疗耐受性较差.     

吸入异维甲酸用于预防肺癌的疗效观察

目的探讨吸入异维甲酸能够针对靶细胞发挥足够药效的方法,同时避免全身性中毒.方法给白鼠腹腔注射一次性剂量的氨基钾酸脂或二苯骈(a)芘(BaP)或特异亚硝胺类化合物4-甲基亚硝胺-1(3-吡啶基)-1-丁酮(NNK).从第2天开始,将白鼠分别置于浓度为1.3,20.7,481 mg/L的异维甲酸气雾剂中45 min.置于低浓度异维甲酸中的白鼠每日1次,中等浓度的异维甲酸剂量1周3次,置于高浓度异维甲酸中的白鼠1周2次.结果测到的总沉积剂量分别为0.24,1.6,24.9 mg/kg,据估算,其中16%沉积在肺部.肺部药物剂量的每周沉积量的计算结果分别为以前给接受过氨基钾酸脂的白鼠进行治疗而未能发生作用的口服剂量的0.01%,0.07%和1.1%.10～16周以后,解剖白鼠,统计肺部增生和肿瘤的数量.对于所有的致癌物质,接受高剂量异维甲酸的白鼠,肿瘤的多样性出现了56%～80%(P＜0.005)的降低;接受中等剂量异维甲酸的白鼠,肿瘤的多样性出现了67%～88%(P＜0.005)的降低;接受小剂量治疗的经过BaP和NNK处理的白鼠,多样化的降低程度分别为30%(P＜0.13)和16% (P＜0.30),差异无显著性.在接受BaP和NNK的白鼠中,增生区域的数量与剂量呈正相关,而与肿瘤数量成反比,表明有抑制作用.相对于接受乙醇吸入的白鼠,吸入中等剂量异维甲酸可以引起肺组织的维甲酸受体(RAR)的变化,具体表现为RARα(3.9倍于乙醇组)、RARβ(3.3倍)和RARγ(3.7倍).结论维甲酸受体是该系统内的类维生素A活性的有效生物标志,吸入异维甲酸有利于有肺癌高发危险的人群预防肺癌.     

肺癌新靶点药物研究进展

肺癌的新靶点药物是近几年临床研究和关注的热点,主要有表皮生长因子受体(EGFR)阻断剂、单克隆抗体、诱导分化剂、抗肿瘤血管生成药物、肿瘤耐药逆转剂以及抗肿瘤疫苗等,与化疗联合可以提高疗效.     

Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer

In vitro studies suggest that a deficient mismatch repair (MMR) system reduces 5-Fluorouracil cytotoxicity. Colon cancer (CC) in hereditary nonpolyposis colorectal cancer (HNPCC) is due to a dysfunctioning MMR gene that leads to microsatellite instability (MSI). Clinical studies on the efficacy of 5-Fluorouracil (5-FU) in MSI high tumours are contradictory. In a retrospective study, we compared the survival of subjects with stage III CC from HNPCC families that were treated with and without adjuvant 5-FU. The Dutch HNPCC family registry was used. Information on adjuvant chemotherapy for stage III CC was obtained from subjects of families with a mutation and/or who fulfilled the AMS criteria or who were strongly suspicious for HNPCC. CC specific survival was calculated. Observation time was measured either until the date of death, date of a second primary CC or until the closing date of the study, i.e., June 1, 2001. Statistical analysis was done by Kaplan-Meier survival analysis. A total of 92 subjects with stage III CC were included. Twenty-eight of them (17 males) had adjuvant treatment with 5-FU. The median follow-up was 4 (range: 1-17) years; 8 subjects died of CC. The 5-year survival was 70% (95% Cl: 49-90). Sixty-four subjects (36 males) did not have adjuvant therapy. Their median follow-up was 6 (range: 0-23) years. Twenty of them died of CC. The 5-year survival in this group was also 70% (95% Cl: 59-83). To date, the selection of patients with CC for 5-FU treatment is based on the stage rather than the biology of the tumour. In our study, the 5-year survival of subjects treated with and without adjuvant 5-FU did not differ. Further studies are necessary to elucidate the role of MSI in 5-FU treatment of MSI-H tumours in HNPCC.     

图像引导放疗在58例肺癌患者中的应用观察

目的 观察图像引导放疗(IGRT)在肺癌中的应用价值.方法 搜集近1年内采用IGRT的58例肺癌病例,其中左肺癌22例,右肺癌30例,肺癌纵隔淋巴结转移5例,椎体转移1例.比较摆位前后IGRT数据,比较大体肿瘤体积(GTV)在IGRT图像与模拟定位CT图像的变化.结果 摆位误差在x、y、z轴上分别为(0.02±0.26)、(-0.14±0.49)、(-0.13±0.27)cm和旋转轴上的分别为-0.15°±1.59°、-0.01°±1.50°、0.12°±1.08°.15例IGRT图像显示GTV有移位,其中左上肺最多见有5例.向腹方向移位9例,4例为左上肺病变.23例疗中GTV缩小,其中右上肺10例,左上肺5例.16个病变有在右方向上缩小,其中右上肺7个.22个病变均呈非对称性缩小,GTV平均缩小4.9 cm3.GTV缩小时放疗剂量为4～46 Gy,其中9例为20～30 Gy.结论 IGRT的应用明显减少了肺癌患者放疗摆位误差.IGRT观察到25.9%GTV有移动,44.2%疗中GTV缩小,何时进行靶区修改有待进一步研究.     

5-fluorouracil steady state pharmacokinetics and outcome in patients receiving protracted venous infusion for advanced colorectal cancer

PVI 5FU gives increased response rates and reduced toxicity when compared to bolus 5FU (J Clin Oncol 1989, 425-432). PVI 5FU administration was reported to give highly variable (>1000-fold) plasma 5FU concentrations at steady state (FU Css) which correlated with toxicity (Ann Oncol 1996, 47-53); but only 19 patients were studied. Therefore, we performed a study of PVI 5FU in 61 patients with advanced colorectal cancer to assess the variability (inter- and intra-subject) in 5FU Css associated with PVI 5FU (300 mg m(-2)day(-1)) and to attempt to correlate pharmacodynamic end-points (anti-tumour activity, toxicity) with 5FU Css as a prelude to 'exposure-guided' 5FU administration. All 5FU sampling was performed between 10 am and noon. PVI 5FU administration continued to 26 weeks in patients with disease improvement or stabilization. The response rate was 26% (33% stable disease) and median survival was 11 months. Hand-foot syndrome was the most common dose limiting toxicity. Variability in 5FU(300)Css was considerably less than previously reported; 94 +/- 25 ng ml(-1)(CV = 27%). No relationships were demonstrated between subject mean 5FU(300)Css and PD end-points such as response, mucositis, diarrhoea and hand-foot syndrome. The lack of correlation suggests that measurement of 5FU concentrations should not be used to individualize dosing in patients receiving PVI 5FU for advanced colorectal cancer.     

肺癌组织中错配修复基因mRNA表达

目的 探讨ＤＮＡ错配修复（ＭＭＲ）基因ｍＲＮＡ在肺癌组织中冢其与微卫星６改变关系。方法 用ＲＴ－ＰＣＲ和ＰＣＲ－变性聚丙烯酰胺凝胶电泳－银染法,检测４６原发性肺癌组织中５种ＭＭＲ基因ｍＲＮＡ表达及６种微卫星改变。结果 ５种ＭＭＲ基因ｍＲＮＡ在肺癌组织中表达降你的发生庇为１３．０％～３２．６％,至少一种基因ｍＲＮＡ表达降爸的发生率为５８．７％（２７／４６）。３９．１％（１８／４６）病例有至少２种基因     

肺癌脑转移立体定向放疗后MRI变化及对近期疗效评价影响

目的 评价肺癌脑转移SRT后MRI变化及对RECIST下疗效的影响。方法 回顾分析SRT的31例肺癌脑转移病例的60个病灶,评价疗后MRI表现及按RECIST记录的疗效。结果60个病灶SRT后MRI评价如下:(1)14个病灶复发,其中8个结节状强化增强、5个均匀强化、1个不均匀强化;(2)11个病灶(18%)为可疑进展,其中均匀强化5个、不均匀强化3个、厚壁强化2个、结节状强化1个;(3) 35个病灶控制,其中19个体积缩小或消失,10个体积和疗前变化不明显,6个较疗前体积增大;(4)有效率为76.7%(可疑进展+控制病灶)。RECIST评价结果为15个病灶CR (25%)、9个病灶PR (15%)、12个病灶SD (20%)、24个病灶PD (40%),有效率为40%。结论 肺癌脑转移SRT后影像学表现多样,且18%病灶难以根据MRI变化判断性质;RECIST低估了近期疗效。     

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.     

5—FU联合甲酰四氢叶酸钙治疗进展期胃肠道癌肿

１９８８年起我们对５５例未能根治的进展期胃肠道瘤肿病人进行了５—ＦＵ与甲酰四氢叶酸钙联合化疗。在可评价３４例中（结直肠癌２４例，胃癌１０例），ＣＲ７例．ＰＲ１３例，总有效率５８．８２％，中位效应持续时间１１月。其中１２例曾接受５—ＦＵ化疗无效，改用本方案后获ＣＲ２例，ＰＲ４例，有效率为５０％。毒副反应主要在胃肠道和造血系统，５—ＦＵ缓慢滴注对提高疗效和减少毒副反应有重要意义。此方案值得进一步推广采用。     

肺癌术后呼吸衰竭26例分析

目的　探讨肺癌术后呼吸衰竭的原因、预防及治疗。方法　对我院1990年1月至1997年10月肺癌术后发生呼吸衰竭的26例患者均进行了机械通气治疗,19例行气管切开术。结果　术后呼吸衰竭发生率4.7%(26/558),死亡率23.1%(6/26)。结论　呼吸道感染、手术创伤、伤口疼痛刺激、术前心肺功能异常等是引起术后呼吸衰竭的主要原因。尽早诊断、及时行气管切开术并给予机械通气是抢救成功的最有效手段,加强围手术期呼吸道管理、避免手术并发症是预防术后呼吸衰竭的关键。     

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study

Background. Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. Methods. This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m², given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m². Leucovorin 10 mg/m² was administered six times, every 6 h, starting 24 h after MTX administration. Results. Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. Conclusions. This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer. Received: August 24, 2001 / Accepted: October 19, 2001     

129例肺癌重复癌的临床分析

目的　分析肺癌重复癌的临床特点与预后。方法　 12 9例第一原发非肺癌的肺癌重复癌第一原发癌与原发肺癌确诊的间隔时间为 10天至 317个月 (中位时间 4 9个月 ) ,Ⅰ、Ⅱ、Ⅲ和Ⅳ期分别有 11、2 9、75和 14例。原发肺癌单纯手术治疗 30例 ,单纯放射治疗 5 4例 ,单纯化疗 8例 ,手术加放射治疗 12例 ,放射治疗加化疗 2 0例 ,手术加化疗 4例 ,手术加放射治疗加化疗 1例。结果　全组 2、3和 5年生存率分别为 4 0 .2 %、2 7.2 %和 15 .3% ,Ⅰ、Ⅱ、Ⅲ和Ⅳ期的 2年生存率分别为 71.6 %、6 0 .7%、32 .9%和 0 % (χ2 =30 .0 8,P <0 .0 1)。Ⅱ期手术治疗 (2 0例 )和非手术治疗 (9例 )的 2年生存率分别为 73.9%和 33.3% (χ2 =6 .4 5 ,P <0 .0 5 )。两病变间隔 >4 9个月者和≤ 4 9个月者的 2年生存率分别为 4 3.2 %和 37.4 % (χ2 =0 .80 ,P >0 .0 5 )。结论　第一原发非肺癌的肺癌重复癌与原发性肺癌的临床特点与预后相似 ,失败原因主要为肺肿瘤 ,病期与能否手术治疗是影响预后的因素。