吉西他滨联合奥沙利铂或替吉奥对比吉西他滨单药治疗晚期胰腺癌临床观察

目的：在真实临床背景下,比较吉西他滨联合奥沙利铂或替吉奥对比吉西他滨单药治疗晚期胰腺癌的疗效和不良反应。方法87例晚期胰腺癌患者分为三组：吉西他滨单药组（ G组）23例,吉西他滨1000 mg · m－2,静滴30 min,第1、8天。吉西他滨联合奥沙利铂组（GM组）33例,在G组基础上联合奥沙利铂130 mg· m－2,第1天。吉西他滨联合替吉奥胶囊组（ GS组）31例,在G组基础上联合口服替吉奥胶囊80／100／120 mg· d－1,每天2次,第1～14天;三组均每21 d为一周期。每2～3个周期进行评价。结果三组比较,其有效率（RR）、疾病控制率（DCR）和临床受益率（CBR）均未取得统计学意义（P＞0．0167）;GM组和GS组的中位无进展生存（PFS）和中位总生存时间（OS）均明显高于G组,差异有统计学意义（P＜0．0167）;而GM组和GS组比较,虽后者略显优势,但差异无统计学意义（P＞0．0167）。三组患者的主要不良反应为血液学毒性和消化道反应,联合化疗组的末梢神经损害和皮疹发生率略高于单药组,但差异不显著（ P＞0．05）。结论在真实临床背景下,GM方案和GS方案较吉西他滨单药治疗晚期胰腺癌可获得更好的生存期,且不良反应可以耐受,二者均可作为首选治疗方案。     

吉西他滨联合化疗在晚期胰腺癌中的疗效观察

目的探讨吉西他滨（GEM）联合化疗在治疗晚期胰腺癌中的疗效观察。方法回顾分析45例晚期胰腺癌患者的临床资料,采用吉西他滨联合奥沙利铂的化疗方案。结果 45例均可评价,总有效率为33.3%。中位生存期（MST）：7.5个月。1年生存率为35%,2年生存率为25%。结论 GEM联合奥沙利铂治疗晚期胰腺癌能可以明显改善生活质量,不良反应少,可作为一线治疗方案,进行推广[1]。     

吉西他滨单药与多西他赛单药治疗老年晚期非小细胞肺癌的临床研究

目的 观察吉西他滨单药与多西他赛单药一线治疗老年晚期非小细胞肺癌的疗效及不良反应.方法 分析55例老年晚期非小细胞肺癌患者,吉西他滨单药化疗29例,多西他赛单药化疗26例,评价疗效及不良反应.结果 55例无CR病例,吉西他滨组PR 8例,SD 11例,PD 10例,中位生存期为5.5个月;多西他赛组PR 7例,SD 12例,PD 7例,中位生存期为6个月.两组比较RR及中位生存期差异无统计学意义（P＞0.05）.多西他赛组中性粒细胞减少及消化道黏膜反应的发生率略高于吉西他滨组.结论 吉西他滨单药与多西他赛单药治疗老年晚期非小细胞肺癌疗效相当,但吉西他滨不良反应的发生率低.     

吉西他滨单药与吉西他滨联合化疗治疗晚期胰腺癌的临床观察

目的分析吉西他滨单药化疗与吉西他滨联合化疗治疗晚期胰腺癌的临床效果。方法120例晚期胰腺癌患者,按照自主抽签法分为对照组和观察组,各60例。对照组应用吉西他滨单药化疗治疗,观察组实施吉西他滨联合化疗治疗。比较两组患者的临床疗效及毒副反应发生情况。结果观察组患者治疗总有效率为93.33%,对照组患者治疗总有效率为78.33%;观察组患者治疗总有效率显著高于对照组,差异有统计学意义(P<0.05)。观察组患者血液系统毒副反应发生率为35.00%,消化系统毒副反应发生率为40.00%;对照组血液系统毒副反应发生率为15.00%,消化系统毒副反应发生率为8.33%;观察组患者血液系统毒副反应发生率及消化系统毒副反应发生率均高于对照组,差异有统计学意义(P<0.05)。结论将吉西他滨作为化疗基础,加用合顺铂、奥利沙铂等药物对晚期胰腺癌患者进行联合化疗,可起到改善病情和提升存活率的效果,在临床中的可行性较大,值得宣传推广。     

替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌的临床效果分析

目的 分析替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌的临床效果.方法 74例老年晚期胰腺癌患者,根据用药方案不同分为观察组和对照组,各37例.观察组采取替吉奥单药治疗,对照组采取吉西他滨单药治疗.比较两组临床疗效、不良反应发生率、生存时间.结果 两组总缓解率比较差异无统计学意义(P>0.05).观察组不良反应发生...     

单药吉西他滨治疗老年晚期肺癌的临床研究

目的通过使用吉西他滨治疗老年晚期肺癌,了解吉西他滨单药使用对肺癌晚期症状的改善。方法从医院50例老年晚期肺癌患者进行随机选择,分为治疗组与对照组,进行不同方案治疗。结果维持治疗与对照组的TTP分别为2.9与1.8个月,有统计学意义,总生存期分别为为13.5和11.8。结论老年晚期肺癌患者接受单药吉西他滨治疗可延长疾病的进展期,生存期可延长,可接受药物不良反应。     

吉西他滨联合替吉奥对比吉西他滨单药三线治疗晚期非小细胞肺癌的疗效及安全性

目的观察吉西他滨联合替吉奥方案对比吉西他滨单药方案三线治疗晚期非小细胞肺癌的疗效及安全性。方法收集我院2012年6月~2014年6月进行三线治疗的晚期非小细胞肺癌患者68例,其中38例接受吉西他滨联合替吉奥化疗,30例接受吉西他滨单药化疗。采用RE-CIST 1.1版标准评价化疗有效率,采用美国国立癌症研究所毒性判定标准(NCI-CTCAE)4.0评价毒性反应。结果吉西他滨联合替吉奥组的有效率、中位无进展生存时间和总生存时间均高于吉西他滨单药组。联合化疗组骨髓抑制、胃肠道反应、口腔黏膜炎及疲乏发生率较单药组高,但主要为I~II级毒性反应。结论吉西他滨联合替吉奥三线治疗晚期非小细胞肺癌优于吉西他滨单药,耐受性良好,可作为晚期非小细胞肺癌三线治疗的选择。     

替吉奥联合吉西他滨与单药吉西他滨治疗进展期胰腺癌的疗效比较

目的 评价吉西他滨单药以及与替吉奥联合治疗局部晚期或转移性胰腺癌的有效率、临床受益反应（评价指标包括患者的疼痛强度、止痛药物消耗量、体力状况评分和体重变化）、生存时间和不良反应。方法 回顾性分析2009年1月至2011年10月收治的62例晚期胰腺癌患者,分为吉西他滨单药组（30例）和吉西他滨＋替吉奥联合组（32例）。单药组：吉西他滨1 000 mg·m-2、第1,8天,静脉滴注30 min,每3周重复。联合组：吉西他滨用法同单药组,替吉奥口服2次·d-1,第1~14天,每3周重复。结果 62例患者均可评价客观疗效,可评价临床受益反应者56例（单药组27例,联合组29例）。单药组和联合组有效率分别为23.3％和31.3％（P〈0.05）,临床受益率分别为59.2%和72.4%（P〉0.05）。2组6个月生存率分别为60.0%和68.7%（P〉0.05）,1年生存率分别为26.6%和31.2%（P〉0.05）。中位无疾病进展时间（PFS）分别为3.9个月和5.4个月（P〈0.05）,中位总生存时间分别为7.8个月和9.1个月（P〉0.05）。2组不良反应比较差异无统计学意义（P〉0.05）。结论 吉西他滨联合替吉奥与单药吉西他滨治疗晚期胰腺癌安全有效,前者有效率优于后者。在延长生存期方面也显示出一定的优势,但该差异无统计学意义。     

三维适形放疗联合单药吉西他滨同步放化疗治疗晚期胰腺癌的临床价值

目的分析三维适形放疗联合单药吉西他滨同步放化疗治疗晚期胰腺癌的临床价值。方法选取36例晚期胰腺癌患者,回顾患者临床资料,给予三维适形联合单药吉西他滨同步放化疗治疗,分析患者治疗效果。结果 36例患者近期疗效总有效率为66.7%,毒副反应在Ⅱ^Ⅲ度,表现为骨髓抑制及胃肠道反应,治疗后生存质量明显提高,疼痛程度明显减轻,与治疗前对比(P<0.05)。结论三维适形联合单药吉西他滨同步放化疗治疗晚期胰腺癌的临床疗效值得肯定,可延长患者生存期,不良反应轻,值得临床进一步推广及使用。     

吉西他滨联合替吉奥治疗晚期转移性胰腺癌的临床疗效和安全性评价

目的评价吉西他滨(GEM)联合替吉奥(tegafur)方案与GEM单药方案治疗晚期转移性胰腺癌的临床疗效及安全性。方法入选晚期转移性胰腺癌患者51例,随机分为GEM组24例和GEM+tegafur组27例。GEM组给予静脉滴注吉西他滨1 g·m-2,第1,8,15天给药,28 d为1周期,连续4个周期;GEM+tegafur组静脉滴注吉西他滨1 g·m-2,第1,15天给药,同时口服替吉奥80 mg·m-2·d-1,28 d为1周期,连续4个周期。疗程结束后,分析比较2组患者客观疗效及不良反应发生率。结果 GEM组客观有效率为25.0%,疾病控制率为45.8%;GEM+tegafur组客观有效率为37.0%,疾病控制率为74.1%。2组患者客观有效率差异无统计学意义(P>0.05),但GEM+tegafur组疾病控制率高于GEM组,差异有统计学意义(P<0.05)。GEM+tegafur组Ⅲ~Ⅳ级粒细胞减少、恶心呕吐及腹泻发生率分别为7.4%,11.1%和3.7%;GEM组为8.3%,12.5%和4.2%,2组患者的主要不良反应发生率差异无统计学意义(P>0.05)。结论吉西他滨联合替吉奥可提高晚期转移性胰腺癌的疾病控制率,且不增加不良反应。     

Squalenoyl gemcitabine nanomedicine overcomes the low efficacy of gemcitabine therapy in pancreatic cancer

Development of chemoresistance and rapid inactivation of gemcitabine (Gem), the standard therapy for advanced pancreatic cancer, are responsible of the major therapeutic failures. To overcome the above drawbacks we designed a novel nanomedicine strategy for Gem nanoparticle (NP) formulation based on squalene conjugation. The purpose was to investigate the antitumor efficacy of gemcitabine-squalene (SQ-Gem) NPs on chemoresistant and chemosensitive pancreatic adenocarcinoma models. Cell viability and apoptosis assays showed that SQ-Gem NPs displayed higher antiproliferative and cytotoxic effects, particularly in chemoresistant Panc1 tumor cells. In in vivo studies, compared to native Gem, SQ-Gem NPs decreased significantly the tumor growth, prevented tumor cell invasion, and prolonged the survival time of mice bearing orthotopic pancreatic tumors. These results correlate with a greater reduction of Ki-67 and induction of apoptosis. These findings demonstrate the feasibility of utilizing SQ-Gem NPs to make tumor cells more sensitive to Gem and thus provide an efficient new therapeutic alternative for pancreatic adenocarcinoma. FROM THE CLINICAL EDITOR: Pancreatic malignancies represent some of the most notoriously treatment resistant cancer varieties. This paper discusses a novel and promising nanotechnology-based treatment approach, currently at the basic science stage.     

盐酸吉西他滨的处方前研究

目的测定盐酸吉西他滨在不同pH缓冲液中的平衡溶解度以及在正辛醇-水和正辛醇-缓冲液体系中的表观油水分配系数,并对其水溶液的稳定性进行研究。方法采用HPLC法测定盐酸吉西他滨的含量,摇床法测定该药物的表观溶解度和油水分配系数。结果 25℃条件下,盐酸吉西他滨在水中的平衡溶解度为58.82 g.L-1,在酸性介质中的平衡溶解度相对增加;盐酸吉西他滨的表观油水分配系数LgP为-1.22;60℃条件下,盐酸吉西他滨水溶液在pH3.84~10.37内较稳定,pH小于2或pH大于11时,降解反应加快,药物含量明显下降。结论盐酸吉西他滨的水溶性较强,其水溶液在强酸和强碱环境下不稳定。     

吉西他滨膀胱灌注化疗的临床研究

目的探讨吉西他滨膀胱灌注预防非肌层浸润性膀胱癌(NMIBC)术后复发的疗效和安全性。方法选择90例NMIBC患者,经尿道膀胱癌电切术(TUR-BT)后,随机分成3组,每组30例。G1组给予1 000 mg吉西他滨膀胱灌注,G2组给予2 000 mg吉西他滨膀胱灌注,P组给予吡柔比星30 mg膀胱灌注。观察并比较三组的肿瘤复发率及不良反应。结果随访3~24个月,中位随访15个月。G1组、G2组、P组的2年肿瘤复发率分别为13.33%、16.67%、43.33%,G1组、G2组的肿瘤复发率低于P组(P<0.05),但G1组、G2组比较差异无统计学意义(P=0.72);三组不良反应发生率分别为23.33%、26.67%、33.33%(P>0.05)。不良反应主要表现为尿频、尿急、尿痛等膀胱刺激症状,经过对症治疗后缓解,均未发生严重的不良反应。结论吉西他滨膀胱灌注化疗在预防NMIBC术后复发方面疗效较好,有较高的临床价值。     

DNA repair mechanisms involved in gemcitabine cytotoxicity and in the interaction between gemcitabine and cisplatin

The influence of DNA repair mechanisms on the interaction between gemcitabine and cisplatin was studied using a panel of Chinese hamster ovary (CHO) cell lines deficient in one of the following repair pathways: base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). NER and HR are known to be involved in platinum-DNA adduct repair. Single agent experiments demonstrated that each of the repair deficient cell lines had a similar sensitivity towards gemcitabine as the parental cell lines, whereas the NER- and HR-deficient lines showed increased sensitivity towards cisplatin. Furthermore, in the parental cell lines, the administration sequence cisplatin followed by gemcitabine was synergistic, whereas the reversed schedule showed additivity and simultaneous administration revealed antagonistic cytotoxicity. In the repair deficient cell lines, using this synergistic schedule of cisplatin followed by gemcitabine, loss of synergy was observed in the NER- and HR-deficient cell lines. However, the magnitude of the effect in the NER-deficient cells was small. The sensitivity to the combination of cisplatin and gemcitabine shown by the BER- and NHEJ-deficient cell lines did not differ significantly from that of the parental cell line. Cellular accumulation of platinum as well as the formation of GG- and AG-intrastrand adducts in the parental line and in the HR-deficient line were not affected by gemcitabine.In conclusion, our results indicate that BER, NER, HR, and NHEJ are most likely incapable of modulating the cytotoxicity of gemcitabine, and that HR is involved in the synergistic interaction between cisplatin and gemcitabine in our cell system.     

HPLC法测定盐酸吉西他滨原料及其注射用制剂的有关物质

目的采用梯度洗脱的HPLC法测定盐酸吉西他滨原料及其注射用制剂的有关物质,并利用LC-MS对碱破坏后得到的未知杂质进行进一步研究。方法使用CB色谱柱,以不同比例的0．14mol·L^-1磷酸盐缓冲液（pH2．5±0．1）和甲醇分别为流动相A和B,梯度洗脱,流速1．0mL·min^-1,二极管阵列检测器,检测波长275nm。结果吉西他滨主峰和各杂质峰均达到基线分离;胞嘧啶和吉西他滨分别在质量浓度0．4676—4．676mg·L^-1和0．4164—4．164mg·L^-1内呈良好线性,r分别为1．0000和0．9998;盐酸吉西他滨的最低检测限为0．1249ng。LC-MS结果显示碱破坏后得到的两个未知杂质为吉西他滨的同分异构体。结论本方法灵敏、准确,专属性强,为分析各个厂家的药品质量提供了一个科学合理的评价体系。     

SL-01, an oral gemcitabine derivative, inhibited human cancer growth more potently than gemcitabine

SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 on the growth of human cancers with gemcitabine as control. Experiments were performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 induced the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In in vivo studies, we evaluated the efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively delayed the growth of NCI-H460 and HCT-116 without significant loss of body weight. Molecular analysis indicated that the high efficacy of SL-01 was associated with its ability to induce apoptosis as evidenced by increase of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in cancer cells. These biological activities of SL-01 were more potential than that of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as a potent oral anticancer agent that may supplant the use of gemcitabine in the clinic.     

盐酸吉西他滨的合成路线图解

吉西他滨具有抗瘤谱广、毒副反应低等特点,被广泛应用于各种实体肿瘤的治疗,尤其是对胰腺癌和非小细胞肺癌有显著的疗效。公开报道的吉西他滨的合成路线多且杂,因此,很有必要将其合成路线进行归纳整理,方便人们查阅以及做出相应的工艺优化。     

磁性吉西他滨隐形纳米脂质体的制备及其理化性质

目的:研究制备磁性吉西他滨隐形纳米脂质体(MGSL)的最佳条件.并对其质量进行检测.方法:通过逆相蒸发法制备MGSL,采用扫描电镜和原子力显微镜时其形态进行观察;利用激光粒度分析仪测定MGSL粒径大小和粒度分布;通过高效液相色谱法检测药物的栽药量和包封率;使用专业磁性测试仪进行体外磁响应性测定,且对MGSL的稳定性进行评价.结果:MGSL为圆形或椭圆形,大小均匀一致,其平均粒径为206.6 nm,粒度分布窄,大小均匀.MGSL载药量为(10.4±0.7)%,包封率为(81.7±5.1)%.并具有体外磁响应性好、稳定性高等特点.结论:本法制备的MGSL符合纳米磁靶向给药系统的条件,有望成为一种有效的抗肿瘤物质.     

Clinical pharmacology and pharmacogenetics of gemcitabine

Gemcitabine is a cytotoxic nucleoside analog, which is widely used in the treatment of malignancies. Interindividual differences in gemcitabine pharmacokinetics and pharmacodynamics have been demonstrated. Pharmacogenetic factors may account for a significant proportion of these differences. This review provides an update on the pharmacogenetics of gemcitabine and its influence on gemcitabine efficacy and toxicity.