吉西他滨联合顺铂与吉西他滨单药化疗治疗晚期胰腺癌比较的Meta分析

目的：通过Meta分析.探讨吉西他滨联合顺铂和吉西他滨单药化疗在治疗晚期胰腺癌的意义.方法：通过MEDLLNE,EMBASE,ASCO论文集等数据为检索国内外已发表和未发展的相关文献,选择治疗组为吉西他滨联合铂化疗,对照组为吉西他滨单药化疗的晚期县级腺癌对照试验（randomized controlled trial RCT）.由两位评委者分别按上述检索策略收集资料,按铵入标准入选,主要对生存率进行Meat分析,其次是客观缓解率和毒副反应.结果：共纳入6个RCT,吉西他滨联合顺铂化疗与吉西他滨单药化疗比较,装卸生存率无差别（P=0.25）,临床获益反应率无差别（P=0.58）,客观缓解率提高6%（P=0.08）,血小板减少症增加8%（P=0.17）,恶心/呕吐增加11%（P=0.07）,但均无统计学意义.结论：现有证据不推荐吉西他滨联合铂治疗晚期胰腺癌,吉西他滨单药化疗仍是目前的标准治疗.     

吉西他滨联合顺铂或奥沙利铂治疗晚期非小细胞肺癌87例

[目的]比较吉西他滨联合顺铂或奥沙利铂治疗晚期非小细胞肺癌(NSCLC)的疗效和毒副反应。[方法]87例晚期NSCLC患者分为两组:顺铂组42例,吉西他滨1000mg/m2,d1,d8;顺铂25mg/m2,d1～d3。奥沙利铂组45例,吉西他滨1000mg/m2,d1,d8;奥沙利铂130mg/m2,d1。28d/周期。评价有效率、疾病进展时间和毒副反应。[结果]顺铂组与奥沙利铂组的有效率分别为28.6%和31.1%(P=0.8),中位疾病进展时间分别为6.2个月(4.0~8.5个月)和5.7个月(4.5~7.8个月)(P=0.07)。两组主要毒副反应为胃肠道反应、周围神经毒性及骨髓毒性。顺铂组胃肠道反应的发生率(81.0%)明显高于奥沙利铂组(51.1%)(χ2=8.6,P=0.0)。奥沙利铂组的周围神经毒性的发生率(57.8%)明显高于顺铂组4.8%(χ2=28.0,P=0.0)。[结论]吉西他滨联合顺铂或奥沙利铂是晚期NSCLC的有效方案,均可作为晚期NSCLC的一线治疗方案。     

吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效比较

目的：比较吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效。方法：前瞻性分析了2002年3月-2005年8月收治的56例局部晚期胰腺癌患者的疗效，其中26例采用吉西他滨联合适形放疗（放化组），30例采用吉西他滨联合顺铂（化疗组）。结果：可评估病例54例，放化组有效率（CR＋PR）为68．O％，化疗组有效率（CR＋PR）为37．9％，两组差异有统计学意义（P=0．0275）。放化组和化疗组的6月生存率分别为84．O％和62．1％（P=0．0728）；12月生存率分别为64．O％和37．9％（P=0．0561）。两组差异无统计学意义。放化组和化疗组的临床获益率（CBR）分别为84．0％和69．0％，两者差异无统计学意义（P=0．1976）。放化组和化疗组的严重不良事件总发生率分别为36．0％和44．8％，无统计学差异（P=0．5103）。结论：在近期疗效方面，吉西他滨联合适形放疗的近期疗效优于吉西他滨联合顺铂；而远期生存率，吉西他滨联合适形放疗虽然显示出一定的优势，但无统计学意义，二者在CBR和严重不良事件发生率无明显差异。     

吉西他滨单药或联合顺铂治疗高龄晚期非小细胞肺癌临床研究

目的为了比较吉西他滨单药与联合顺铂治疗晚期非小细胞肺癌(non-small cell lungcancer,NSCLC)的疗效、生活质量及毒副反应,探索治疗高龄NSCLC的更好方案。方法对61例70岁以上高龄晚期NSCLC随机分为两组。单药组吉西他滨1000mg/m2,静脉滴入,d1、d8。联合组吉西他滨同上,加用顺铂70mg/m2,静脉滴入,d1。两组均3周重复。结果单药组有效率26.7%。KPS评分下降率6.7%。联合组有效率为38.7%,KPS评分下降率为32.3%。两组有效率差异无统计学意义,u=1.92,P=0.0541,而KPS评分下降率差异有统计学意义,u=3.237,P=0.0016。结论吉西他滨单药治疗晚期高龄NSCLC疗效与联合顺铂方案相似,但联合组明显降低生活质量。     

晚期胰腺癌调强放疗同步吉西他滨化疗的临床观察

为了评价局部晚期胰腺癌调强放疗同步吉西他滨化疗的临床观察。分析我院2006-09-02-2009-08-02收治的86例局部晚期胰腺癌患者的近期疗效、毒副反应和长期生存率。将所有患者随机分为治疗组(46例)和对照组(40例),其中治疗组,采用调强放疗同步吉西他滨化疗;对照组采用单纯吉西他滨化疗。治疗组和对照组有效率(CR+PR)分别为67.4%和37.5%,近期疗效两组差异有统计学意义,χ2=4.859 8,P=0.023。治疗组和对照组的6个月生存率分别为82.6%和60.0%,P=0.058;12个月生存率分别为60.9%和35.0%,两组间差异无统计学意义,P=0.056。两组的临床获益率(CBR)差异无统计学意义,P=0.058。两组消化系统不良反应差异有统计学意义,P=0.042。初步研究结果提示,调强放疗同步吉西他滨同步化疗治疗局部晚期胰腺癌,在近期疗效方面优于吉西他滨单药治疗,而远期生存率虽有一定的优势,但两者在临床获益方面差异无统计学意义,同步放化疗组消化系统毒副反应有增加的趋势,但在可控制范围内。     

吉西他滨单药或联合顺铂治疗高龄晚期非小细胞肺癌临床研究

目的：为了比较吉西他滨单药与联合顺铂治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的疗效、生活质量及毒副反应,探索治疗高龄NSCLC的更好方案.方法：对61例70岁以上高龄晚期NSCLC随机分为两组.单药组：吉西他滨1 000 mg/m^2,静脉滴入,d1、d8.联合组：吉西他滨同上,加用顺铂70 mg/m^2,静脉滴入,d1.两组均3周重复.结果：单药组有效率26.7%.KPS评分下降率6.7%.联合组有效率为38.7%, KPS评分下降率为32.3%.两组有效率差异无统计学意义,u=1.92, P=0.054 1,而KPS评分下降率差异有统计学意义,u=3.237, P=0.001 6.结论：吉西他滨单药治疗晚期高龄NSCLC疗效与联合顺铂方案相似,但联合组明显降低生活质量.     

吉西他滨单药及联合顺铂治疗老年晚期非小细胞肺癌临床观察

目的:观察吉西他滨单药及联合顺铂在老年晚期非小细胞肺癌的临床疗效及不良反应.方法:76例晚期老年非小细胞肺癌随机分为两组,吉西他滨联合顺铂组(GP)36例,吉西他滨单药组(G)40例.结果:GP组总有效率为36.1%,中位生存期(MST)为9.2个月,疾病缓解时间(DRT)为4.0个月;单药(G)组分别为30.0%,8.6个月及4.3个月,两组间差异无统计学意义(P＞0.05).在生存质量改善方面,GP组一般状况KPS评分增加3例、稳定14例,G组增加11例、稳定24例,两组间差异无统计学意义(P＞0.05);GP组体重增加7例、稳定13例,G组增加15例、稳定21例,两组间差异有统计学意义(P＜0.05).最常见的不良反应为骨髓抑制,主要表现为白细胞及血小板下降,GP组和G组Ⅲ度～Ⅳ度反应发生率分别为11.1%、7.5%,2.7%、5.0%,差异无统计学意义(P＞0.05);GP组发生Ⅲ度～Ⅳ度恶心呕吐反应19例,占52.7%,明显高于单药G组(P＜0.05),其余不良反应轻微,可耐受.结论:吉西他滨单药与吉西他滨联合顺铂治疗老年晚期非小细胞肺癌疗效相似,但不良反应轻,有助于提高生活质量,吉西他滨单药化疗更适合于老年晚期非小细胞肺癌的治疗.     

吉西他滨联合多西他赛或顺铂治疗晚期尿路上皮移行细胞癌的临床研究

目的比较吉西他滨联合多西他赛与联合顺铂治疗晚期尿路上皮移行细胞癌的疗效及安全性,探讨吉西他滨的联合用药方案。方法 43例病理证实的晚期尿路上皮移行细胞癌(膀胱癌37例,肾盂癌4例,输尿管癌2例)随机分成吉西他滨联合多西他赛组(GD组)和吉西他滨联合顺铂组(GC组)。GD组22例给予吉西他滨联合多西他赛化疗,GC组21例给予吉西他滨联合顺铂化疗。治疗至疾病进展或出现不能耐受的毒性反应停止,依据RECIST标准评价疗效,依据NCI CTC标准评价毒性,随访36个月。结果 3例因毒性反应退出试验,40例可评价疗效,其中GD组21例,GC组19例。GD组CR 1例,PR 7例,有效率38.1%,SD 6例,临床获益66.7%,平均疾病进展期为9个月,平均存活时间为16.5个月。GC组无CR,PR 6例,有效率31.6%,SD 7例,临床获益68.4%,平均疾病进展期为10个月,平均存活时间为15.7个月。两组在有效率和临床获益间的差异无统计学意义(P>0.05)。43例患者均可评价毒性,毒副反应主要为粒细胞减少、贫血、血小板减少、食欲减退和疲乏。结论吉西他滨联合多西他赛与传统方案吉西他滨联合顺铂治疗晚期尿路上皮移行细胞癌疗效相似,毒副反应可以耐受,是一种患者可接受的治疗方案。     

吉西他滨联合顺铂或卡铂治疗晚期非小细胞肺癌的近期疗效

目的 :观察吉西他滨 (gemcitabine)联合顺铂与吉西他滨联合卡铂治疗晚期非小细胞肺癌的疗效和毒性反应。方法 :10 6例经病理组织学或细胞学证实的晚期非小细胞肺癌患者分为GP和GC两组 ,GP组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;顺铂 30mg/m2 ,静滴 ,第 1～ 3天。GC组应用吉西他滨 10 0 0mg/m2 ,静滴 ,第 1、8天 ;卡铂ACU =5 ,静滴 ,第 1天。 2 1天为 1个周期 ,连用 2个周期评价疗效。结果 :GP组和GC组有效率 (CR PR)分别为 4 8.1%和 4 4 .2 % (P >0 .0 5 ) ;中位疾病进展时间分别为 6 .8个月和 6 .2个月 (P >0 .0 5 ) ;毒性反应中GP组消化道毒副反应较GC组大 ,差异有显著性 ;骨髓毒性两组相当 ,差异无显著性。结论 :吉西他滨联合顺铂及吉西他滨联合卡铂两方案治疗晚期非小细胞肺癌疗效均较好 ,毒性反应轻微 ,患者耐受良好 ,尤其吉西他滨联合卡铂的消化道反应轻 ,患者易于接受 ,值得临床进一步研究。     

吉西他滨单药与联合顺铂化疗治疗中老年晚期非小细胞肺癌的疗效观察

目的:评价吉西他滨联合顺铂治疗非小细胞肺癌(NSCLC)与单独使用吉西他滨的疗效与安全性.方法:140例晚期NSCLC(Ⅲb/Ⅳ期)患者随机均分为吉西他滨联合顺铂组(n=70)和单独使用吉西他滨组(n=70).联合给药组患者静脉注射吉西他滨(1 250 mg/m2,第1、8天)和顺铂(75 mg/m2,第1天);单独给药组患者静脉注射吉西他滨(1 250 mg/m2,第1、8天).每21天为一个疗程,共持续4个疗程.结果:吉西他滨与顺铂联合给药组疗效优于吉西他滨单独给药组(P＜0.05).而在血细胞减少、血红蛋白减少以及恶心呕吐等不良反应上,吉西他滨单独给药组低于联合给药组,但组间比较差异无统计学意义(P＞0.05).治疗后2年的随访结果也显示经吉西他滨与顺铂联合治疗的患者1年有效率及中位生存期均优于吉西他滨单独治疗组(P＜0.05).结论:吉西他滨联合顺铂治疗中老年晚期非小细胞肺癌疗效确切,未明显增加不良反应,患者耐受性好,值得临床推广.     

Pharmacogenetics and pharmacoepigenetics of gemcitabine

Gemcitabine (2′,2′-difluoro 2′deoxycytidine, dFdC) is an analog of cytosine with distinctive pharmacological properties and a wide antitumor-activity spectrum. The pharmacological characteristics of gemcitabine are unique because two main classes of genes are essential for its antitumor effects: membrane transporter protein-coding genes, whose products are responsible for drug intracellular uptake, as well as enzyme-coding genes, which catalyze its activation and inactivation. The study of the pharmacogenetics and pharmacoepigenetics of these two gene classes is greatly required to optimize the drug’s therapeutic use in cancer. This review aims to provide an update of genetic and epigenetic bases that may account for interindividual variation in therapeutic outcome exhibited by gemcitabine.     

Vasculitis due to gemcitabine

We report the first occurrence of gemcitabine-induced vasculitis. It concerns a 45-year-old man diagnosed with non-small lung cancer since 2 months. After the first cycle of chemotherapy, consisting of gemcitabine and cisplatin, he developed myalgia and swelling of arms and legs with impairment of movement. This re-occurred during the second cycle of chemotherapy. Further anemia, elevated ESR and increased creatininephosphokinase. A surgical biopsy showed leucocytoclastic vasculitis and necrosis of muscle tissue. The chemotherapy was stopped and the complaints disappeared and did not return.     

Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer

Background:

An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.

Methods:

Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m⁻² plus vinorelbin 25 mg m⁻² on days 1+8 (GemVin), or plus cisplatin 30 mg m⁻² on days 1+8 (GemCis), or plus capecitabine 650 mg m⁻² b.i.d. orally days 1–14 (GemCap), q3w. The primary end point was response rate.

Results:

A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ⩾grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand–foot syndrome in 2.0% of the GemCap patients (per patient analysis).

Conclusions:

This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.     

Cell cycle effects of gemcitabine.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine, or dFdC) is a promising anticancer agent with demonstrated clinical activity in solid tumours currently undergoing clinical trials. Despite extensive studies on the biochemical mechanism of action, cell cycle perturbations induced by dFdC have not yet been thoroughly investigated, apart from the expected inhibition of DNA synthesis. The aim of our study was to clarify whether cell population kinetics is a vital factor in the cytotoxicity of dFdC in single or repeated treatments and in the dFdC-cisplatin combination. Ovarian cancer cells growing in vitro were treated with dFdC for 1 hr in a range of concentrations from 10 nM to 10 microM. Cell kinetics was investigated by DNA-bromodeoxyuridine flow cytometry, using different experimental protocols to measure either the time course of DNA-synthesis inhibition or the fate of cells in G(1), S or G(2)M at the time of dFdC treatment or 24 hr later. A modified sulforhodamine B test was used to assess the growth inhibition caused by dFdC given alone or with cisplatin. Although dFdC promptly inhibited DNA synthesis, cytotoxicity on proliferating cells was not specific for cells initially in the S phase. DNA synthesis was restored after a G(1) block of variable, dose-dependent length, but recycling cells were intercepted at the subsequent checkpoints, resulting in delays in the G(2)M and G(1) phases. The activity of repeated treatment with dFdC + dFdC or dFdC + cisplatin was highly dependent on the interval length between them. These results suggest that the kinetics of cell recycling from a first dFdC treatment strongly affects the outcome of a second treatment with either dFdC itself or cisplatin.     

Role of gemcitabine in cancer therapy

Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising new cytotoxic agents. The drug has shown activity in a variety of solid tumors, and has been approved for the treatment of non-small cell lung cancer, pancreatic, bladder, and breast cancer. Recent data showed that gemcitabine is also active against ovarian cancer. Gemcitabine has a good toxicity profile, with myelosuppression being the most common side effect, while non-hematological events are relatively uncommon. The low toxicity profile makes the drug a valid option for unfit and elderly patients. Due to the synergistic activity with other chemotherapeutic compounds, mainly cisplatinum, several trials have been conducted to evaluate the efficacy and tolerability of gemcitabine in combination with other cytotoxic agents. Current clinical trials are evaluating the role of gemcitabine in combination with new targeted therapies.     

Radiation recall reaction following gemcitabine

A case of dermatitis and myositis in the upper thorax following administration of gemcitabine in a 65-year-old woman with metastatic non small cell lung cancer (NSCLC) is described. The reaction and time course suggest a radiation recall phenomenon. This report joins a small but increasing number of radiation recall events related to gemcitabine. The possibility of a radiation recall reaction should be borne in mind when a patient develops symptoms in a previously irradiated site without evidence of disease progression at that site. Cessation of the precipitating drug is the most important step in management and systemic steroids may hasten symptomatic relief.