Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinomaTian-Jie Qin,Xin-Han Zhao,Jun Yun,Ling-Xiao Zhang,Zhi-Ping Ruan,Bo-Rong Pan

AIM:To evaluate the efficacy and safety of gemcitabine-oxaliplatin(GEMOX)cornbined with huachansu(cinobufagin)injection treatment in patients with locally advanced or metastatic gallbladder carcinoma(GBC),and to assess the quality of life(QOL)of such patients.METHODS:Twenty-five patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine(1000 mg/m2)over 30 min on days 1 and 8,2 h infusion of oxaliplatin(120 mg/m2)on day 1,and 2-3 h infusion of huachansu(20 mL/m2)on days-3-11,every 3-4 wk.Treatment was continued until occurrence of unacceptable toxicity or disease progression.QOL of patients was assessed by the EORTC QLQ-C30 at baseline,at the end of the first,third and sixth chemotherapy cycles,and 1 mo after the treatment.RESULTS:Among the 25 patients with a median age of 64 years(range 42-78 years),23 were evaluable in the study.A total of 137 cycles of therapy were performed and the median cycle was 5(range 1-8)per patient.Out of the 23 patients whose response could be evaluated,8 partial responses(PR)were observed(34.8%),while 7 patients(30.4%)demonstrated a stable disease(SD).The disease control rate was 65.2%.Progression of cancer was observed in 8(34.8%)patients.The median progression-free and overall survival time was 5.8 mo(95% CI:4.5-7.1 mo)and 10.5 mo,respectively.The therapy was well tolerated,with moderate myelosuppression as the main toxicity.Anemia grade 2 was seen in 16.0%,neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients,respectively.Non-hematologic toxicity ranged from mild to moderate.No death occurred due to toxicity.The QOL of patients was improved after chemotherapy,and the scores of QOL were increased by 10 t0 20 points.CONCLUSION:GEMOX combined with huachansu(cinobufagin)injection is well tolerated,effective,thus ireproving the QOL of patients with advanced GBC.(C)2008 The WJG Press.All rights reserved.     

二甲双胍联合奥沙利铂抗肿瘤作用

目的:探究二甲双胍联合奥沙利铂对结肠癌移植瘤小鼠的抗肿瘤作用。方法:32只BALB/C雄性小鼠左前肢腋下接种c26小鼠结肠腺癌细胞,随机分为恶病质组、二甲双胍组、奥沙利铂组以及联合组,另外8只小鼠作为正常组。奥沙利铂组小鼠每周1次腹腔注射奥沙利铂注射液0.01 mg/g,同时每日灭菌蒸馏水0.1 m L/g灌胃;二甲双胍组小鼠每日给予二甲双胍0.2 mg/g灌胃,同时每周1次腹腔注射生理盐水0.02 m L/g;联合组小鼠每日给予二甲双胍0.2 mg/g灌胃,同时每周1次腹腔注射奥沙利铂注射液0.01 mg/g;正常组和恶病质组小鼠每日灭菌蒸馏水0.1 m L/g灌胃,同时每周1次腹腔注射生理盐水0.02 m L/g。每日检测小鼠体重、肿瘤大小、自发性活动、精神毛发等。连续给药42 d后,颈椎脱臼法处死小鼠,解剖分离并称重右下肢腓肠肌组织,ELISA法检测腓肠肌组织炎症因子水平,HE染色观察腓肠肌形态。结果:荷瘤小鼠体重、腓肠肌质量、腓肠肌横切面积较正常组均明显降低(均P0.05),奥沙利铂组和联合组小鼠肿瘤重量及体积均明显减少,且联合组减少最为明显(均P0.05),各荷瘤小鼠腓肠肌组织中IL-6及TNF-α水平较正常组均明显升高,其中二甲双胍组及联合组较恶病质组则明显下降(均P0.05)。结论:二甲双胍联合奥沙利铂能够抑制肿瘤生长,且能延缓癌性恶液质的发生。     

奥沙利铂联合替吉奥治疗进展期小肠腺癌的临床分析

目的：分析奥沙利铂联合替吉奥治疗进展期小肠腺癌的临床效果,探索进展期小肠腺癌新的化疗方法。方法选取我院肿瘤治疗中心收治的23例进展期小肠腺癌患者为研究对象,给予奥沙利铂85 mg·m-2第1天静脉滴注,每3周为1个周期;替吉奥口服40 mg·m-2,每日早晚饭后各1次,连续2周,停药1周,每3周为1个周期。定期随访,治疗2~4周期后评价患者的治疗效果、不良反应及生活质量。结果23例患者至少接受2个周期的奥沙利铂联合替吉奥方案化疗,0例完全缓解,6例部分缓解,10例病情稳定,7例病情进展,客观缓解率为26.09％,临床获益率为69.57％。中位无进展生存时间为6.3个月,中位总生存时间为18.2个月。根据KPS评估生活质量,13例改善,6例稳定,4例恶化。不良反应主要包括骨髓抑制、周围神经病变、胃肠道反应、黏膜炎、肝肾功能损害及皮疹,经过对症处理后均好转,无化疗相关性死亡。结论奥沙利铂联合替吉奥是治疗进展期小肠腺癌的一种新的化疗方法,其疗效较好,不良反应较轻,可在一定程度上改善患者的生活质量,值得进一步大样本研究。     

FOLFOX方案治疗转移性胃癌临床疗效分析

目的探讨FOLFOX方案治疗转移性胃癌临床疗效和不良反应。方法选择我院2008年至2011年收治的经细胞学或组织学证实的转移性胃癌患者35例,接受FOLFOX方案化疗治疗。3～4周期后评价疗效和不良反应,并对患者的生存状况进行随访。结果 35例患者化疗后总有效率为65.7%,内脏转移患者总有效率为59.1%,显著低于淋巴结转移(P<0.05)。随访率为91.4%,中位TTP为6.4个月,中位OS为11.8个月,3年生存率达43.8%。结论 FOLFOX方案治疗转移性胃癌临床疗效显著,毒副作用较轻,能显著提高患者生存率,对淋巴结转移敏感度更高,值得临床推广。     

Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro

It has been established that hyperthermia can enhance cytotoxicity of some chemotherapeutic agents. This has led to various clinical trials of thermochemotherapy, although many questions remain unanswered. The effects of various agents have been studied on animal tumours with different histopathology at elevated temperatures. These studies indicated that alkylating agents were most effective to all tumours at a moderately elevated temperature. Cisplatin was also effective to all tumours, but its effectiveness at 41.5°C was less than that of alkylating agents. To quantitatively study these findings, the magnitude of thermal enhancement of melphalan, an alkylating agent, and that of oxaliplatin, a new platinum compound, were studied at 37-44.5°C by the colony formation assay. The dose of each agent was kept constant, and cell survival was determined as a function of treatment time. The cell survival curve was exponentially related with treatment time at all test temperatures, and the T 0 (the time to reduce survival from 1 to 0.37) decreased with an increasing temperature. These results suggested that the cytotoxic effect of these agents occurred with a constant rate at 37°C, and the rate was facilitated with an increasing temperature. This suggests that heat can accelerate the cytotoxic chemical reaction, leading to substantial thermal enhancement. The thermal enhancement ratio (TER, the ratio of the T 0 at 37°C to the T 0 at an elevated temperature) increased with an increase in the temperature. The activation energy for melphalan at moderately elevated temperatures was largest among the agents tested in the laboratory and that for oxaliplatin was approximately half of the melphalan activation energy. This suggests that the thermal enhancement for the cytotoxicity of melphalan or alkylating agents might be the greatest. Potential mechanisms of thermal enhancement of cytotoxicity were discussed.     

卡培他滨联合方案治疗老年晚期结直肠癌的临床研究

目的评价卡培他滨联合方案治疗老年晚期结直肠癌的疗效与不良反应。方法77例老年晚期结直肠癌患者随机分组，卡培他滨联合组（36例）接受奥沙利铂（L—OHP）加卡培他滨方案化疗，OLF组（41例）接受L-OHP加氟尿嘧啶／亚叶酸钙（FU／CF）方案化疗，观察对比其疗效与不良反应。结果卡培他滨联合组的有效率为41．67％，肿瘤控制率（临床受益率）为77．78％，中位肿瘤进展时间为7．9个月。OLF组的有效率为39．02％，肿瘤控制率为75．61％，中位肿瘤进展时间为7．2个月。两组有效率比较差异无统计学意义（P〉0．05）。不良反应：两组均无严重的化疗相关不良反应，两组患者骨髓抑制、消化道反应、脱发、皮疹、肝肾功能损害、神经毒性的发生率比较差异均无统计学意义（P均〉0．05），卡培他滨联合组手足综合征的发生率较OLF组明显升高（P〈0．05）。结论对老年晚期结直肠癌患者，卡培他滨联合方案与OLF方案疗效相仿，不良反应均可耐受，卡培他滨口服给药缩短了住院时间，提高了老年患者的生活质量，卡培他滨联合方案不失为一种老年晚期结直肠癌患者一线治疗方案的较佳选择。     

香菇多糖联合化疗治疗中晚期消化道肿瘤疗效观察

目的观察香菇多糖联合化疗治疗中晚期消化道肿瘤患者的临床疗效及不良反应。方法67例患者分为对照组33例单用FOLFOX方案,治疗组34例FOLFOX方案前3d开始加用香菇多糖1mg,疗程2周,4周为1周期,2周期评价疗效。结果治疗组CR2例,PR12例,SD11例,有效率为41.2%;对照组CR1例,PR患者12例,SD10例,有效率为39.4%,两组比较无显著差异(P>0.05),且治疗组CD3+、CD4+细胞活性及CD4/CD8比值较治疗前明显提高(P<0.05)。而对照治疗后各免疫细胞指标与治疗前比较无显著性差异(P>0.05)。结论香菇多糖联合化疗治疗老年消化道肿瘤可以提高患者免疫功能,有较好疗效,且不良反应轻。     

多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌47例临床观察

目的观察多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌的近期疗效和不良反应。方法47例晚期胃癌患者采用多西他赛60 mg/m~2,静脉滴注,第1天;奥沙利铂85 mg/m~2,静脉滴注,第2天;卡培他滨2000 mg/m~2,bid,口服,服10 d停4 d,14 d为1周期。3周期后评价疗效和不良反应。结果全组47例患者均可评价疗效,其中CR 4例(8.5%),PR 24例(51.1%),SD 12例(25.5%),PD 7例(14.9%),总有效率59.6%,Ⅲ/Ⅳ度中性粒细胞减少发生率51.1%。中位TTP为6.2个月(3.4～11.6个月),中位OS为11.3个月(5.9～14.6个月)。结论多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌有效率较高,血液学毒性低,近期疗效较好,用药方便、安全,明显提高了患者的生活质量。     

希罗达草酸铂方案联合艾迪治疗进展期胃癌的临床研究

目的 探讨希罗达草酸铂方案联合艾迪治疗进展期胃癌的疗效,生存率及毒副反应.方法 64例经胃镜活检病理学确诊的不能手术或术后复发转移未接受过任何化疗的晚期胃癌,男44例,女性20例,年龄32～74 岁,中位年龄48岁;均为Ⅲ～Ⅳ期,Karnofsky评分≥70分.随机分为2组治疗组和对照组,采用希罗达草酸铂方案联合艾迪注射液,希罗达1250 mg/m2 Bid d1～14 P.O,草酸铂120 mg/m2 5%葡萄糖注射液500 ml,静脉滴注4h,艾迪60 ml 生理盐水400 ml,d1～14,静脉滴注,3周为1疗程,32例进展期胃癌用希罗达草酸铂方案治疗,不加艾迪作为对照组,剂量同上,6个疗程后评估.结果 治疗组32例,CR 1例,PR 22例,PR 70.2%,中位无病生存期7.3个月,中位生存期11.9个月,1年生存率75.2%(24/32),2年生存率22.5%(7/32),卡氏评分比治疗前提高10分,主要副反应为中性粒细胞减少9.3%(3/32),末梢神经木麻15.2%(5/32),手足综合征9.3%(3/32),未出现3级以上的药物相关副反应.对照组RR56.8%,中位无病生存期6.5个月,中位生存期10.1个月,1年生存率为59.2%,2年生存率15.4%,卡氏平分较治疗前无明显变化,中性粒细胞减少15.1%,末梢神经木麻20.8%,手足综合征18.2%.两组生存率、有效率、毒副反应比较有统计学意义(P＜0.05).结论 希罗达草酸铂方案联合艾迪治疗进展期胃癌中位无病生存期,中位生存期及1、2年生存率高,症状得到明显改善,生活质量提高,毒副反应轻,体现中西医结合治疗的优势,在治疗晚期胃癌中安全、可靠,值得推广应用.