替加氟与氟尿嘧啶治疗胃癌的疗效比较

目的:比较替加氟与氟尿嘧啶治疗胃癌的临床疗效和安全性。方法:将62例胃癌患者随机分为观察组(32例)和对照组(30例)。观察组患者给予替加氟片6⁸片,口服,每日3次,3个月为一疗程,休息1个月后重复下个疗程;对照组患者给予氟尿嘧啶注射液108片,口服,每日3次,3个月为一疗程,休息1个月后重复下个疗程;对照组患者给予氟尿嘧啶注射液10²0 mg加入0.9%氯化钠注射液250 ml中,静脉滴注,每日1次,10 d为一疗程,休息20 d后重复下个疗程。两组患者均治疗1年后评价疗效。随访所有患者治疗1年、2年生存率和中位生存期,毒性反应及治疗费用。结果:两组患者总有效率,1年、2年生存率,中位生存期比较,差异均无统计学意义(P>0.05)。观察组患者除恶心、呕吐、腹泻、血小板降低发生率显著低于对照组外,其他不良反应发生率与对照组比较,差异均无统计学意义(P>0.05)。结论:替加氟与氟尿嘧啶治疗胃癌疗效相当,均可有效改善患者生存质量,但替加氟安全性优于氟尿嘧啶。     

Stat3活性降低对人胃癌5-氟尿嘧啶耐药细胞的影响

目的探讨Stat3信号在人胃癌5-氟尿嘧啶(5-Fu)耐药细胞及其亲本细胞中活化水平的差异与胃癌耐药机制的关系。方法分别采用凝胶阻滞电泳法和Western blot法检测人胃癌细胞株SGC7901及其5-Fu耐药细胞株SGC7901／R中Stat3-DNA结合活性的变化和磷酸化Stat3蛋白的表达;半定量逆转录-PCR法检测耐药细胞及其亲本细胞中Stat3和血管内皮生长因子(VEGF)mRNA的表达;免疫细胞化学染色法显示VEGF蛋白在2种细胞内的表达情况。结果耐药细胞及其亲本细胞中有不同程度的Stat3组成性激活和磷酸化Stat3蛋白的表达;与亲本细胞SGC7901相比,耐药细胞SGC7901／R中Stat3-DNA的结合活性水平较低,磷酸化Stat3蛋白的表达减少;耐药细胞中Stat3 mRNA的表达下降,核因子-κB1 mRNA的表达显著上升,而VEGF mRNA及其编码的蛋白水平却较其亲本细胞降低。结论人胃癌5-FU耐药细胞株SGC7901／R中Stat3活性水平降低与其耐药机制相关,且可能与耐药细胞中VEGF表达减少有关。     

吉西他滨联合奥沙利铂或氟尿嘧啶治疗晚期胰腺癌临床观察

目的观察吉西他滨联合奥沙利铂(GEMOX方案)与吉西他滨联合氟尿嘧啶(GF方案)治疗晚期胰腺癌的近期疗效和不良反应。方法经病理组织学或细胞学证实的40例胰腺癌患者,随机对照分为GEMOX组和GF组,各20例。可评价疗效分别为15例和14例。GEMOX组给予吉西他滨1000mg/m2加生理盐水100ml,静脉滴注30min,第1,8,15d;奥沙利铂50mg/m2,静脉滴注,第1,8,15d。GF组给予吉西他滨1000mg/m2加生理盐水100ml,静脉滴注30min,第1,8,15d,氟尿嘧啶500mg/m2加5%葡萄糖液(GS)500ml,静脉滴注6h以上,第1~5d。结果两组患者性别、肿瘤病理类型及TNM分期具可比性。GEMOX组部分缓解(PR)2例,微效(MR)3例,稳定(D)6例,进展(PD)4例,治疗有效率达33.3%,中位生存期8.7个月,临床受益率(CBR)50.0%,肿瘤标志物CA19-9下降>50%占47.1%。GF组PR2例,MR3例,SD5例,PD4例,治疗有效率达35.7%,中位生存期10.1个月,CBR38.9%,CA19-9下降>50%占38.9%。经统计学比较,两组CBR差异有显著性(P<0.05)。主要不良反应为白细胞减少和血小板减少。结论吉西他滨联合奥沙利铂或联合氟尿嘧啶的治疗有效率、CBR较高,中位生存期较长,不良反应小。GEMOX的CBR较GF更高。     

Phase II clinical trial of advanced and metastatic gastric cancer based on continuous infusion of 5-fluorouracil combined with epirubicin and oxaliplatin

PURPOSE: To evaluate the efficacy and tolerability of systematic treatment of unresectable advanced or metastatic gastric cancer (A/MGC) based on EOF5 regimen (the combination of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil). PATIENTS AND METHODS: Twenty-six patients (18 males, 8 females; age range, 35-72 years) with histologically confirmed metastatic (n = 23) or unresectable advanced (n = 3) gastric adenocarcinoma with (n = 6) or without previous chemotherapy (n = 20) were consented to receive EOF5 (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1, followed by continuous infusion of 5-fluorouracil 375-425 mg/m(2) day(-1) on day 1-5), and the treatment cycle was repeated every 3 weeks. Responses to treatment and toxicity were evaluated every 2 cycles. RESULTS: In the first-line treatment group of 20 patients, complete (CR) and partial (PR) remission were observed in two (10%) and six (30%) patients, respectively with an overall response rate of 40%). Eleven (55%) patients showed stable (SD) and one (5%) progressive disease (PD). One-year survival rate, time to progression (TTP) and median overall survival (OS) were 45%, 9.7 and 12.5 months, respectively. In the second-line treatment group of six patients, the numbers of CR, PR, SD and PD were 0, 1, 4 and 1, respectively. Symptomatic response rates were 88.2, 76.9, 89.5, and 88.9% for abdominal pain, distention, anorexia and weight loss. The mean Karnofsky performance status score was increased (P < 0.001) and maintained after two and four cycles treatment. The major adverse events were nausea/vomiting, oral mucositis, peripheral neuropathy, phlebitis, constipation and myelosuppression. CTC grade 3 or 4 hematologic toxicities included leucopenia (7.7%), neutropenia (15.4%), thrombocytopenia (19.2%), and anemia (3.8%). No treatment-related deaths were recorded. CONCLUSIONS: EOF5 regimen shows good efficacy and an acceptable safety profile in A/MGC patients, and would be a suitable alternative regimen for this indication.     

Pneumatosis cystoides intestinalis after fluorouracil chemotherapy for rectal cancer

Pneumatosis cystoides intestinalis （PCI） is a relatively rare condition characterized by intraluminal gas in the gastrointestinal tract. Several chemotherapeutic agents have been reported to be associated with PCI, although fluorouracil-related PCI is extremely rare. We report a case of a 76-year old man who received adjuvant chemotherapy for rectal cancer with fluorouracil （FU） and leucovorin （LV）. After 1 cycle of the treatment, he presented with diarrhea and abdominal pain. Abdominal radiogram revealed the presence of free air under the diaphragm and intramural gas in the intestine. Laparotomy was performed, showing a suspected diagnosis of perforation in the gastrointestinal tract. Intraoperative findings revealed penumatosis of the intestine without evidence of perforation. He was treated supportively and his symptoms improved. In conclusion, we should consider the possibility of PCI occurring in patients with malignancies during chemotherapy treatment.     

Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating peroxisome proliferator-activated receptor γ

AIM: To examine whether and how rosiglitazone enhances apoptosis induced by fluorouracil in human colon cancer (HT-29) cells.METHODS: Human colon cancer HT-29 cells were cultured in vitro and treated with fluorouracil and/or rosiglitazone. Proliferation and growth of HT-29 cells were evaluated by MTT assay and trypan blue exclusion methods, respectively. The apoptosis of HT-29 cells was determined by acridine orange/ethidium bromide staining and flow cytometry using PI fluorescence staining. The expressions of peroxisome proliferator-activated receptor y (PPARy), Bcl-2 and Bax in HT-29 cells were analyzed by Western blot.RESULTS: Although rosiglitazone at the concentration below 30 umol/L for 72 h exerted almost no inhibitory effect on proliferation and growth of HT-29 cells, it could significantly enhance fluorouracil-induced HT-29 cell proliferation and growth inhibition. Furthermore, 10 umol/L rosilitazone did not induce apoptosis of HT-29 cells but dramatically enhanced fluorouracil-induced apoptosis of HT-29 cells. However, rosiglitazone did not improve apoptosis induced by fluorouracil in HT-29 cells pretreated with GW9662, a PPARy antagonist. Meanwhile, the expression of Bax and PPARy was up-regulated, while the expression of Bcl-2 was down regulated in HT-29 cells treated with rosiglitazone in a time-dependent manner. However, the effect of rosiglitazone on Bcl-2 and Bax was blocked or diminished in the presence of GW9662.CONCLUSION: Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating PPARγ.     

经内镜局部化学治疗晚期食管癌胃癌疗效分析

目的 探讨氟尿嘧啶＋顺铂（5-FU＋DDP）局部化学治疗食管癌、胃癌的近期疗效和副作用。方法 将确诊晚期食管癌、胃癌患者86例随机分为两组，A组48例应用5-Fu250mg＋DDP20mg经内镜分点注射于肿瘤表面和周边，B组38例应用5-Fu500mg＋DDP40mg静脉滴注，内镜下观察对肿瘤的直接影响及对食管内梗阻的影响。结果 A组和B组有效率分别为60．42％、39．47％（P〈0．05），中位生存期分别为9．8个月和7．6个月。主要副反应为白细胞减少和胃肠道反应，无治疗相关死亡病例。结论 5-FU＋DDP联合局部化疗晚期食管癌胃癌有效，可改善患者的生活质量，延长生存期。     

进展期胃癌术中应用氟尿嘧啶缓释剂间质化疗的临床疗效

目的评价进展期胃癌根治术中植入5-FU缓释剂间质化疗的临床疗效和安全性。方法 102例进展期胃癌患者(术前均经胃镜和病理检查确诊)随机分为治疗组和对照组,各51例。2组均行D2根治术,治疗组在手术结束时局部植入5-FU缓释剂进行间质化疗,术后4周进行6个周期常规化疗;对照组术中不进行腹腔内干预性治疗,术后化疗方案同治疗组。结果 2组患者的腹腔引流量、白细胞水平、白蛋白水平及消化道不良反应方面的差异均无统计学意义(P>0.05);中位随访时间为28个月,治疗组肿瘤局部复发率低于对照组(16.3%比39.1%,P<0.05),治疗组术后3年的总生存率高于对照组(85.8%比67.3%,P<0.05)。结论进展期胃癌行D2根治术时植入5-FU缓释剂进行间质化疗无明显不良反应,能减少局部复发率,提高患者生存率,是治疗胃癌行之有效的方法。     

术中局部植入氟尿嘧啶缓释剂治疗原发性肝细胞癌

目的 探讨肝癌根治术中植入氟尿嘧啶缓释剂的安全性及其对无瘤生存率和总体生存率的影响.方法 收集2008年1月至2009年1月完成肝癌根治手术的患者59例,按术中有无使用氟尿嘧啶缓释剂分为治疗组(24例)和对照组(35例),两组患者术后均未予其他化疗.检测两组患者术前1天、术后3周的白细胞、肝功能、AFP;术后半年内每月、半年后每3个月复查AFP及影像学,对可疑复发的患者行CT引导下穿刺活检确诊,统计术后6、12、18、24个月的无瘤生存率和总体生存率.结果 术后3周治疗组WBC、ALT、AST、TBIL,与对照组差异无统计学意义(分别t=0.801、-0.854、- 1.948、- 0.503,均P＞0.05).治疗组术前、术后3周、术后6个月AFP为(361.58±431.06) μg/L、(17.02±15.55)μg/L、(43.61±58.03) μg/L,对照组为(495.50±441.63) μg/L、(26.82±60.46) μg/L、(127.48±229.79) μg/L.术后6个月治疗组明显低于对照组(t=-2.065,P＜0.05).治疗组术后6、12、18、24个月的无瘤生存率为95.8％、91.7％、79.2％、75.0％,对照组为94.3％、71.4％、60.0％、48.6％(Log rank检验x2=4.035,P＜0.05);治疗组术后6、12、18、24个月的总体生存率为100％、95.8％、91.7％、83.3％,对照组为100％、94.3％、77.1％、60.0％(Log rank检验x2=3.931,P＜1.05).结论 术中植入氟尿嘧啶缓释剂具有良好的安全性,是降低肝癌复发率、延长患者生存期的有效方法.     

紫杉类联合顺铂+氟尿嘧啶治疗局部晚期头颈部鳞癌效果的系统评价

目的系统评价紫杉类联合顺铂+氟尿嘧啶与顺铂+氟尿嘧啶比较治疗局部晚期头颈鳞癌的有效性和安全性。方法计算机检索h e Cochrane Library(2013年第1期)、PubMed、EMbase、Web of Science、CBM、CNKI、VIP和WanFang Data数据库,收集所有紫杉类联合顺铂+氟尿嘧啶与顺铂+氟尿嘧啶比较诱导化疗治疗局部晚期头颈鳞癌的随机对照试验(RCT),检索时限均从建库至2013年4月1日。由2位评价员按纳入与排除标准独立筛选文献、提取资料并评价质量后,采用RevMan 5.2软件进行Meta分析。结果共纳入7个RCT,2088例患者,其中紫杉类联合顺铂+氟尿嘧啶诱导化疗组(TPF组)1051例,顺铂+氟尿嘧啶诱导化疗组(PF组)1037例。Meta分析结果显示:TPF组与PF组在1年总生存率[RR=1.12,95%CI(1.02,1.23),P=0.02]、2年总生存率[RR=1.20,95%CI(1.11,1.29),P<0.00001]、3年总生存率[RR=1.18,95%CI(1.07,1.31),P=0.0007]、1年无进展生存率[RR=1.18,95%CI(1.08,1.28),P=0.0002]、2年无进展生存率[RR=1.20,95%CI(1.06,1.36),P=0.003]、3年无进展生存率[RR=1.48,95%CI(1.25,1.74),P<0.00001]、完全缓解率[RR=1.67,95%CI(1.26,2.23),P=0.0004]和总反应率[RR=1.18,95%CI(1.11,1.27),P<0.00001]方面差异均有统计学意义,TPF组均优于PF组。在不良反应方面,与PF相比,TPF组中性粒细胞减少症发生率[RR=1.42,95%CI(1.24,1.63),P<0.00001]、脱发发生率[RR=16.09,95%CI(4.59,56.38),P<0.0001]和中性粒细胞减少性发热发生率[RR=2.21,95%CI(1.29,3.80),P<0.004]更高。结论紫杉类联合顺铂+氟尿嘧啶诱导化疗治疗局部晚期头颈鳞癌具有较好的治疗效果,但不良反应较多。