大肠癌根治术中联合应用缓释氟尿嘧啶疗效的评价

目的:评价缓释氟尿嘧啶应用于大肠癌根治术中的疗效.方法:结直肠癌患者100例,随机分为治疗组与对照组.治疗组术中于瘤床等处植入缓释氟尿嘧啶,每例总计800mg.术后对每位患者连续随访监测36个月,评价其用药后不良反应、复发转移率、生存率等疗效指标.结果:术中联合应用缓释氟尿嘧啶并未增加对造血、免疫、肝肾等的不良反应;且术中联合应用缓释氟尿嘧啶后明显降低了治疗组使用者的局部与全身复发转移率,提高了生存率,治疗组复发转移率以及生存率与对照组的差异有显著性.结论:术中联合应用缓释氟尿嘧啶是一种安全可提高结直肠癌患者生存率的方法.     

奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期大肠癌的临床疗效

大肠癌是人类常见恶性肿瘤之一 ,近几年在我国特别是大城市发病率有上升趋势。复发、转移是死亡的主要原因。我们自 1999年 3月 - 2 0 0 2年 4月用奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期大肠癌共 2 5例 ,现报告如下。1　材料与方法1.1　病例选择　 2 5例均经病理证实 ,其中结肠癌 18例 ,直肠癌 7例 ;男性 16例 ,女性 9例 ;年龄 2 8岁～ 71岁 ;2 2例为术后复发转移 ,3例为晚期未切除 ,都有可测量的病灶 ;既往均经过 5 - Fu/ CF为主方案的化疗 ;4周内无其他抗肿瘤治疗 ,预计生存 3个月以上 ,全身状况评分 70分以上 ,化疗前血常规、肝肾功…     

乳腺癌改良根治术中氟尿嘧啶植入剂缓释化疗的临床疗效及安全性

目的:探讨乳腺癌改良根治术中区域性氟尿嘧啶植入剂缓释化疗的临床疗效及安全性。方法:将已行乳腺癌改良根治术患者94例随机分为植入组 48 例及对照组 46 例。两组手术方法相同,植入组在腋窝、锁骨下血管区域、胸大小肌之间多点撒入氟尿嘧啶植入剂,总剂量为400~600 mg;对照组无植入。两组均行常规术后化疗、放疗及内分泌治疗。观察两组并发症、不良反应及临床疗效,随访复发及生存情况。结果:并发症及不良反应发生率两组无统计学差异（P＞0.05）。植入组5年局部复发率明显低于对照组（35.4% vs 47.8%,P=0.016）;5年生存率明显高于对照组（81.3% vs 58.6%,P=0.041）。结论:乳腺癌改良根治术患者术中植入缓释氟尿嘧啶安全、有效,可减少乳腺癌术后局部复发,提高远期生存率,是乳腺癌术后局部化疗的有效途径。     

晚期大肠癌低剂量氟尿嘧啶及顺铂治疗近期疗效

[目的]研究低剂量5氟尿嘧啶/顺铂(5 Fu/DDP)联合方案持续输注治疗晚期大肠癌的疗效及毒副反应。[方法]30例晚期大肠癌予以5 Fu250mg/m2·d,顺铂8mg/m2·d,通过输液泵控制滴速持续性输注18h,以21d为一个疗程 ,休息10d后重复 ,2个疗程评定疗效及毒副作用。[结果]30例晚期大肠癌中 ,CR4例(13.3%) ,PR12例(40.0%) ,CR +PR53.4 % ,毒副作用为骨髓抑制 ,恶心呕吐 ,粘膜炎及腹泻 ,但都为Ⅱ度以下毒副反应。[结论]DDP作为5 Fu的生物化学调节剂 ,与低剂量5 Fu联合应用 ,其近期疗效高 ,毒副作用低 ,有望广泛应用于晚期大肠癌的临床治疗中     

国产奥沙利铂联合氟尿嘧啶、甲酰四氢叶酸钙治疗复发转移大肠癌的疗效观察

目的 观察国产奥沙利铂联合氟尿嘧啶、甲酰四氢叶酸钙治疗复发转移大肠癌的近期疗效及毒副反应。方法 对16例曾行手术且术后化疗后复发转移的晚期大肠癌予L—OHP130mg／m^2静脉滴注4小时第一天，CF200mg／m^2静滴2小时第1～5天，5—Fu 2．15g／m^2加入便携式静脉化疗泵持续120小时静滴，L—OHP前30分钟予恩丹西酮镇吐，每例患均接受3周期化疗后评价疗效。结果 全组16例无CR、PR31．2％(5/16)、SD50％(8/16)、PD18．8％(3／16)，总RR31．2％(5116)。外周神经毒性75％(12／16)，恶性呕吐68．7％(11/16)，腹泻43．7％(7/16)，口腔溃疡37．5(6／16)，贫血37．5％(6/16)，白细胞下降31．2％(5/16)，血小板下降25％(4／16)，肝功能损害31．2(5/16)。结论 国产奥沙利铂联合氟尿嘧啶、甲酰四氢叶酸钙可作为复发转移大肠癌较好的治疗方案。     

食管癌根治术中植入5-氟尿嘧啶缓释粒子行间质化疗的疗效观察

目的探讨食管癌根治术中植入5-氟尿嘧啶缓释粒子行局部化疗的临床疗效和安全性。方法将107例确诊食管癌患者随机分为单纯食管癌根治术组（对照组,n=53）和食管癌根治术中植入5-氟尿嘧啶缓释粒子组（植入组,n=54）,比较两组患者手术前后实验室指标、术后并发症和3年生存率等情况。结果对照组与植入组在治疗前后实验室指标、组间并发症发生率、组间术后1年生存率比较,差异无统计学意义均（P〉0．05）;植入组术后3年生存率（61．11％）优于对照组（39．62％）（P〈0．05）：植入组术后3年局部复发率（18．52％）低于对照组（45．28％）（P〈0．05）。结论食管癌根治术中植入5－氟尿嘧啶缓释粒子能够将药物直接植入病灶部位以维持缓慢释放高浓度状态,提高药物敏感期肿瘤细胞的杀伤力,从而改善患者的临床症状和提高远期生存率,值得临床继续研究和探讨。     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的：研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应，并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较。方法：经病理确诊的晚期大肠癌83例分为以下两组：治疗组行奥沙利铂(oxalipatin)130mg／m^2静脉滴注，第1天给药：氟尿嘧啶(5-FU)425mg／m^2静脉滴注，第1-5天给药；亚叶酸钙(CF)100mg／m^2静脉滴注，第1～5天给药；每3周重复。对照组行氟尿嘧啶(5-FU)42h5mg／m^2静脉滴注,第1～5天给药；亚叶酸钙(CF)100mg／m^2。静脉滴注，第1-5天给药；每3周重复。每例患者至少完成两个周期。结果：治疗组有效率为46．5％，常见的毒性反应为神经毒性；对照组有效率为17．5％，与治疗组差别有统计学意义，未见神经毒性，其他毒性与治疗组无统计学差异。结论：奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好，毒副反应较轻，疗效高于氟尿嘧啶加亚叶酸钙方案。     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的:研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应,并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较.方法:经病理确诊的晚期大肠癌83例分为以下两组:治疗组行奥沙利铂(oxaliplatin)130mg/m2静脉滴注,第1天给药;氟尿嘧啶(5-FU)425mg/m2静脉滴注,第1～5天给药;亚叶酸钙(CF)100mg/m2静脉滴注,第1～5天给药;每3周重复.对照组行氟尿嘧啶(5-FU)425mg/m2静脉滴注,第1～5天给药;亚叶酸钙(CF)100mg/m2静脉滴注,第1～5天给药;每3周重复.每例患者至少完成两个周期.结果:治疗组有效率为46.5%,常见的毒性反应为神经毒性;对照组有效率为17.5%,与治疗组差别有统计学意义,未见神经毒性,其他毒性与治疗组无统计学差异.结论:奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好,毒副反应较轻,疗效高于氟尿嘧啶加亚叶酸钙方案.     

缓释氟尿嘧啶在胃肠恶性肿瘤术中的应用

[目的]探讨区域性缓释化疗在消化道恶性肿瘤中的疗效。[方法]68例胃肠肿瘤患者随机分为两组：治疗组38例,术中使用植入缓释氟尿嘧啶;对照组30例,术中未使用缓释氟尿嘧啶。两组临床病理资料具有可比性。[结果]使用植入缓释氟尿嘧啶治疗组未出现明显的胃肠道反应。治疗组吻合口瘘1例、肠梗阻1例、腹腔化脓性感染1例;而对照组吻合口瘘1例、肠梗阻1例、无腹腔化脓性感染。两组并发症发生率比较无统计学差异（7．9％vs6．7％,χ^2=0．037,19=0．847）。治疗组2年局部复发率为5．3％,而对照组2年局部复发率为23.3％（χ^2=0．060,P=0．027）;两组2年无远处转移率无统计学差异（χ^2=0．060,P=0．807）。治疗组与对照组术后2年生存率分别为94．7％和76．7％（P〈0．05）。[结论]术中植入缓释氟尿嘧啶安全、可行,可降低胃肠肿瘤术后复发率及提高术后生存率．具有一定的临床应用价值。     

乳腺癌术中植入缓释氟尿嘧啶间质化疗的临床研究

0引言乳腺癌是妇女最常见的恶性肿瘤之一,近年来其发病率在全世界范围内呈逐年上升趋势[1].现代乳腺癌治疗模式已形成局部治疗和全身治疗并重的综合治疗模式[2],但全身化疗不良反应明显,且在局部不易形成高浓度,对腋窝淋巴结的影响不大[3].而局部化疗可以在肿瘤部位达到很高的药物浓度,从而更好的发挥化疗药物的抗肿瘤作用[4-5].因此如何选择一种能够有效抑制亚临床病灶,降低复发率的局部化疗方法,成为乳腺癌治疗成败的关键.我们选择术中植入缓释氟尿嘧啶间质化疗,取得了较好的效果,现报告如下.     

L-OHP联合不同使用方法5-FU/FA方案治疗晚期结直肠癌的疗效比较

目的比较L-OHP(奥沙利铂)联合不同使用方法5-FUFA(氟尿嘧啶亚叶酸钙)方案治疗晚期结直肠癌的疗效及不良反应。方法62例患者均可参加疗效评价。ArmA方案(32例):L-OHP130mgm2静滴d1;FA200mg(m2·d),5-FU425mg(m2·d)分别静滴,均d1～5,每3周重复,3周为1周期。ArmB方案(30例):L-OHP85mgm2静滴d1;FA200mg(m2·d)静滴后,5-FU400mg(m2·d)静推,然后5-FU600mg(m2·d)持续微量泵注射22小时,d1～2,每2周重复,4周为1周期。结果ArmA方案CR1例,PR14例,总有效率46.9%。ArmB方案CR1例,PR11例,总有效率40%。严重不良反应较少。结论L-OHP联合不同使用方法5-FUFA方案治疗晚期结直肠癌均有较高疗效,毒副作用相近。     

与食管癌5-FU化疗效果相关分子标记的研究进展

不同个体的食管癌对氟尿嘧啶（Fluorouracil,5-FU）药物疗效存在差异。药物遗传学和药物基因组学的快速发展,使得分子标记指导下的食管癌个体化化疗成为可能,本文对食管癌5-FU疗效预测相关分子标记作一综述。     

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.     

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.     

5-Methyltetrahydrofolate for biochemical modulation of fluorouracil (FU) in patients with advanced colorectal cancer: A randomized phase I--II study of two different FU administration schedules

Background: To determine the maximum tolerable dose (MTD) and therapeutic activity of MTHF-modulated FU using two different administration schedules of the antimetabolite (bolus vs. two-hour infusion), the present randomized study using a 'pick-the-winner' design was undertaken in patients with advanced colorectal cancer.Patients and methods: Eighty-two patients with previously untreated advanced measurable colorectal cancer were randomly assigned to treatment with MTHF (100 mg/m2 days 1–5 i.v. bolus) plus FU (400 mg/m2 days 1–5) given either as i.v. bolus injection or as a two-hour infusion every four weeks. In the absence of dose-limiting toxicity (DLT, defined as WHO grade 3 hematotoxicity and/or WHO grade 2 nonhematologic side effects) and evidence of progressive disease, the FU dose was escalated by 50 mg/m2/day during each subsequent cycle until the individual maximum tolerable dose (MTD) was reached.Results: Forty patients were randomized to the FU bolus arm and 42 patients to the FU two-hour infusion arm. The median MTD was 475 mg/m2/day (95% CI: 450–500) in the FU bolus arm with stomatitis ± diarrhea being the most common DLT. Gastrointestinal side effects were also dose-limiting in the two-hour infusion arm; however, the median MTD was 600 mg/m2/day (95% CI: 568–632). Myelosuppression was more pronounced in the FU bolus arm than in the two-hour infusion arm. The overall response rates were 27.5% (95% CI: 15–44%; 1 CR and 10 PR) for patients treated in the bolus arm and 14.5% (95% CI: 5–28%; 1 CR and 5 PR) for those treated in the two-hour infusion arm. Analogous to recorded response, median time to progression (8.5 vs. 6.25) and overall survival time (14.0 vs. 11.0) tended to be superior in the FU bolus arm.Conclusions: The observed differences in tolerable drug dose and toxicity between the two treatment arms might be explained by the administration schedule-dependent clinical pharmacokinetics of FU and/or the difference in extent of biochemical modulation of the antimetabolite through MTHF. The fact that the two regimens were not equitoxic probably also helps to explain the favourable response activity noted in the MTHF/FU bolus arm. Whether MTHF is as effective as leucovorin for biochemical modulation of FU remains to be determined in a randomized trial, for which we would recommend its combined use with bolus FU ('winner arm') using a starting dose of 400 mg/m2/day ×5.     

COX - 2 与结直肠癌的临床病理参数及 5 - FU 敏感性之间的关系

目的：研究COX-2与结直肠癌临床病理参数之间的关系及对化疗药作用的影响。方法：共纳入100例经病理确诊的新鲜人结直肠癌标本,5-FU的体外敏感实验通过三维微组织块培养法（HDRA）验证。采用免疫组化法检测对应结直癌组织中COX-2表达水平。结果：COX-2表达水平与肿瘤组织的分化程度呈负相关（P=0．05）,与病理分期呈正相关（P=0．02）,与神经侵犯呈正相关（P=0．02）。COX-2表达水平与5-FU药物敏感呈负相关（P=0．02）。结论：COX-2与结直肠癌的分期、分型有关,同时与5-FU的耐药相关。     

Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer

We studied the role of TS (5’VNTR, 5’SNP and 3’UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3’UTR +6 bp/+6 bp (hazards ratio, HR = 2.62, p = 0.007) and ERCC1-118 C/T or C/C (HR = 1.96, p = 0.050) genotypes correlated with a shorter progression free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8 m, 9.6 m and 25.8 m for 0, 1 or 2 FG; p = 0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p = 0.001). In the multivariate analysis, ERCC1-118 (HR = 2.12, p = 0.0037) and TS-3’UTR (HR = 2.68, p = 0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3’UTR +6 bp/+6 bp and ERCC1-118 C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.     

周剂量多西紫杉醇、奥沙利铂联合5-氟尿嘧啶／亚叶酸钙治疗晚期胃癌疗效观察

目的：观察周剂量多西紫杉醇、奥沙利铂联合5-氟尿嘧啶／亚叶酸钙治疗晚期胃癌的近期疗效，毒副作用及生活质量改善情况。方法：18例晚期胃癌患者以多西紫杉醇25mg／m^2d1、d8、d15静脉滴注1小时，奥沙利铂65mg／m2d1、d8静脉滴注3小时，亚叶酸钙100mgd～d5静脉滴注2小时，5-氟尿嘧啶500mg／m^2 d1—d5静脉滴注4小时。4周为1个周期，2周期为1个疗程。所有病人至少接受2周期以上。客观疗效（CR＋PR）和毒副作用按WHO进行评价，生活质量按临床受益反应（cBR）进行评价。结果：18例均可评价疗效，完全缓解（CR）0例，部分缓解（PR）10例，总有效率55．6％，临床受益反应有效率72％，中位唧5．6月。主要毒副反应为骨髓抑制，消化道反应和神经毒性，大部分为Ⅰ～Ⅱ级，可以耐受。结论：每周低剂量多西紫杉醇、奥沙利铂联合5-氟尿嘧啶／亚叶酸钙治疗晚期胃癌近期疗效好，毒副反应轻，耐受性好，病人生活质量明显改善。     

奥沙利铂联合氟尿嘧啶/亚叶酸钙治疗晚期胃癌临床疗效观察

目的:评价奥沙利铂联合5-FU/CF治疗晚期胃癌临床疗效及毒副反应。方法:42例晚期胃癌患者给予奥沙利铂60mg/m2,静滴3~4h,第1天及第8天;CF100mg/m2,静滴2h,d1~d5;5-FU500mg/m2/d,微泵24小时持续泵入d1~d5,21天~28天为1周期。结果:CR2例,PR18例42例总有效率为47.6%。主要的毒副反应为神经性毒性、骨髓抑制和恶心、呕吐,均可耐受,无化疗相关死亡。结论:奥沙利铂联合5-Fu/CF治疗晚期胃癌近期疗效较好,不良反应轻。