吉西他滨联合西妥昔单抗对三阴乳腺癌细胞转移相关基质金属蛋白酶-9(MMP-9)活性的影响

目的：探讨吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、迁移、侵袭的影响，并对可能的机制进行初步的探究。方法：将实验分为西妥昔单抗组（150 μg · mL^-1）、吉西他滨联合用药组（西妥昔单抗150 μg · mL^-1，吉西他滨2.8 μg·mL^-1）。通过MTT、Transwell实验检测联合用药对MDA-MB-231细胞增殖、迁移、侵袭能力的影响，Western blotting实验检测合用药对MDA-MB-231细胞MMP-9、TIMP-1、p-IkB、NF-kB-p65表达水平的影响。结果：吉西他滨联合西妥昔单抗作用MDA-MB-231细胞后，其生长被不同程度的抑制，抑制率随吉西他滨浓度的增加而增高（P<0.05）；联合用药组MDA-MB-231细胞迁移、侵袭数目明显减少（P<0.05），同时MMP-9、p-IkB、NF-kB-p65的表达含量降低，TIMP-1表达含量增加。结论：吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、侵袭、迁移具有抑制作用，并明显抑制MMP-9的表达，其机制可能是通过抑制NF-kB通路实现。     

两种化疗方案治疗晚期非小细胞肺癌的对比观察

目的比较化疗方案GP(吉西他滨和顺铂)和IVP(异环磷酰胺、长春地辛和顺铂)治疗晚期非小细胞肺癌(NSCLC)的疗效和毒性.方法将62例晚期NSCLC患者随机分成两组,治疗组30例,采用GP方案:吉西他滨1000 mg/m^2第1、第8 d静脉滴注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期;对照组32例,采用IVP方案:异环磷酰胺1200 mg/m^2第1～第3 d静脉滴注,长春地辛2.5 mg/m^2第1、第8 d静脉推注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期.2个周期后评价其疗效及毒性.结果治疗组无一例完全缓解,部分缓解6例,总有效率20.0%;对照组亦无一例完全缓解,部分缓解8例,总有效率25.0%.两组无统计学差异(P＞0.05),但治疗组毒性小于对照组.结论双药化疗方案GP治疗NSCLC的疗效不低于三药方案IVP,且毒副作用轻微,更易为晚期肺癌患者所接受.     

吉西他滨联合5-氟尿嘧啶和四氢叶酸治疗晚期胰腺癌的临床研究

目的　评价 5 氟尿嘧啶和四氢叶酸联合化疗与加用吉西他滨后治疗晚期胰腺癌的疗效和不良反应 ;以及 5 氟尿嘧啶药物代谢动力学指标的改变。方法　 43例晚期胰腺癌患者分为实验组 ( 2 2例 )和对照组 ( 2 1例 )。实验组 :吉西他滨 10 0 0mg/m2 ,第 1,8,16天静脉滴注 ,5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 于第 1～ 5天静脉滴注 ;对照组 :5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 在第 1～ 5天静脉滴注 ,均以每 4周为 1疗程 ,持续 4个疗程。结果　实验组完全缓解 (CR) 1例 ( 4 .5 %) ,部分缓解 (PR) 6例 ( 2 7.3 %) ,临床受益反应率 (CBR)为 68.2 %;对照组无CR ,PR3例 ( 14 .3 %) ,CBR有效率 3 3 .3 %。实验组出现不良反应的数量和严重程度较对照组提高且差异具有显著性。实验组 5 氟尿嘧啶血浆药物浓度、血浆峰值提高 ,血浆半衰期延长。结论　吉西他滨与 5 FU、四氢叶酸联合应用治疗晚期胰腺癌有一定的客观疗效 ,可明显改善患者的生存质量 ,但不良反应也随之提高。上述变化与吉西他滨改变 5 FU的药物代谢动力学有关     

NP与GP方案治疗局部晚期非小细胞肺癌近期疗效观察

目的：观察长春瑞宾（NVB）与顺铂（DDP）组成的NP方案和吉西他滨（GEM）与顺铂（DDP）组成的GP方案对局部晚期非小细胞肺癌（NSCLC）的近期疗效和毒副作用。方法：将经病理组织学或细胞学证实的45例局部晚期NSCLC患者随机分为两组,A组（NP方案组）23例,B组（GP方案组）22例,分别给予NVB＋DDP及GEM＋DDP化疗,21天为一周期。结果：A组有效率为47.8%,B组有效率为54.5%,无统计学差异（P〉0.05）。两组毒性反应均以骨髓抑制最为常见,消化道反应和静脉炎亦常见。Ⅲ～Ⅳ度白细胞减少发生率A组为34.8%,B组为31.8%;Ⅲ～Ⅳ度血小板减少发生率A组为4.3%,B组为9.1%。差异均无显著性（P〉0.05）。静脉炎发生率A组为34.8%,B组为0,差异有显著性（P〈0.05）。结论：NP方案和GP方案治疗NSCLC疗效相近,毒性反应均可耐受。     

吉西他滨联合顺铂或氟尿嘧啶治疗晚期胰腺癌临床疗效比较

目的:观察吉西他滨联合顺铂(GP方案)与吉西他滨联合氟尿嘧啶(GF方案)治疗晚期胰腺癌近期疗效和毒副作用的差异。方法:经病理组织学或细胞学证实的60例胰腺癌患者,按照随机对照的原则分为GP组和GF组,各30例。GP组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天;顺铂40mg,静脉点滴,第15、16、17天。GF组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天,氟尿嘧啶500mg/m~2加5％葡萄糖液(GS)500ml,静脉点滴6h以上,第1～5天。结果:GP组部分缓解(PR)3例,微效(MR)5例,稳定(NC)12例,进展(PD)5例,PR+MR达32.0％,中位生存期8.7个月,临床受益率(CBR)57.7％,肿瘤标志物CA19-9下降>50％为48.1％。GF组PR3例,MR8例,NC9例,PD4例,PR+MR达45.8％,中位生存期10.1个月,CBR82.1％,CA19-9下降>50％为53.6％。两组经统计学比较,CBR差异有显著性(P<0.05)。主要毒性反应为白细胞减少和血小板减少。结论:吉西他滨联合氟尿嘧啶以及吉西他滨联合顺铂,较以往单药方案疗效高,副作用少,中位生存期长,CBR高;GP方案和GF方案比较,后者的CBR更高。     

Leucovorin, 5-fluorouracil,and gemcitabine: A phase I study

Gemcitabine is a chemotherapy agent with efficacy in the treatment of lung, pancreas, bladder and breast cancer. It inhibits DNA synthesis by interfering with cytidine triphosphate production and also inhibits the activity of ribonucleotide reductase. Gemcitabine may potentiate fluorouracil's inhibition of thymidylate synthase. This inhibition would be expected to be sequence dependent, occurring only if gemcitabine were administered following fluorouracil (5FU).The combination of leucovorin, 5-FU, and gemcitabine was assessed in this phase I trial. Eligibility requirements included refractory solid tumor malignancy; adequate hematologic, renal and hepatic reserve; no prior therapy with the combination of leucovorin and 5FU, or with gemcitabine; ECOG performance status 0–2, and signed informed consent.Eleven men and nine women were eligible. The median age was 52.5 years and the median performance status was 1. All but three patients had prior chemotherapy. The starting doses were leucovorin 20 mg/m², 5FU 255 mg/m² and gemcitabine 600 mg/m². 5FU and gemcitabine were escalated in tandem to 340 mg/m² and 800 mg/m² and thereafter to 425 mg/m² and 1000 mg/m², respectively. Gemcitabine administration always followed that of 5FU by 30 minutes. The median number of cycles was 2 (range 1–32). Two patients at the starting dose had disease progression within the first cycle with one death on day 28. One patient with cholangiocarcinoma had a partial response and remained on study for 40 months. There were no other responses.The maximum tolerated dose is leucovorin 20 mg/m², 5FU 340 mg/m², and gemcitabine 800 mg/m². The impact of drug sequence remains undetermined.     

吉西他滨联合氟尿嘧啶治疗晚期肝外胆管癌

目的：观察吉西他滨(健择)联台氟尿嘧啶治疗晚期肝外胆管癌的近期疗欢。方法：21例晚期胆管癌患者采用GLF方案化疗：健择1000mg/m^2，静脉滴注30-60分钟，第1，8天给药。亚叶酸钙200mg/m^2，静脉滴注．第1～5天。氟尿啼啶600mg/m^2。静脉滴注2小时．第1～5天。21天为一个两期。结果：21例中无1例达完全缓解，部分缓解5例(23．8％)．稳定8例(381％)。12例(57．14％)患者疼痛得到缓解．生活质量提高。结论：健择联合氟尿嘧啶冶疗晚期无法手术的肝外胆管癌具有较好的近期疗效且不良反应可以耐受。     

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。     

晚期非小细胞肺癌不同治疗方法疗效比较

[目的]评价3种不同方法治疗晚期非小细胞肺癌的疗效.[方法]85例经病理学诊断的晚期肺癌患者随机分为3组,A组(27例)经静脉给药化疗组,B组(30例)单纯支气管动脉灌注化疗组,C组(28例)超选择性支气管动脉栓塞化疗组.3组均采用吉西他滨联合顺铂进行治疗.[结果]近期疗效总有效率56.5%,其中A、B、C 3组分别为40.7%(11/27),56.7%(17/30),71.4%(20/28)(P《0.05).1、2年生存率3组分别为53.8%、30.0%;69.2%、48.2%;83.5%、65.7%,各组间差异有显著性(P《0.05).不良反应主要为骨髓抑制、胃肠道反应,未出现脊髓损伤等严重并发症.[结论]超选择性支气管动脉栓塞化疗是治疗晚期NSCLC的一种安全有效的方法,其疗效优于静脉注射和单纯支气管动脉灌注化疗.     

Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer.

BACKGROUND: Trastuzumab provides significant clinical benefits in HER2-positive metastatic breast cancer patients when administered in combination with chemotherapy. Chemotherapy has also been shown to be beneficial in some patients with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II trial examined the effect of adding trastuzumab to a standard chemotherapeutic combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC. PATIENTS AND METHODS: Patients with untreated stage IIIB/IV HER2-positive NSCLC received up to six 21-day cycles of gemcitabine 1250 mg/m(2) (days 1 and 8) and cisplatin 75 mg/m(2) (day 1). Patients in the trastuzumab arm received trastuzumab 4 mg/kg intravenously (i.v.) followed by 2 mg/kg/week i.v. until progression. RESULTS: Of 619 patients screened, 103 were eligible. Fifty-one patients were treated with trastuzumab plus gemcitabine-cisplatin and 50 with gemcitabine-cisplatin alone. Efficacy was similar in the trastuzumab and control arms: response rate 36% versus 41%; median time to progression 6.3 versus 7.2 months; and median progression-free survival (PFS) 6.1 versus 7 months. Response rate (83%) and median PFS (8.5 months) appeared relatively good in the six trastuzumab-treated patients with HER2 3+ or fluorescence in situ hybridization (FISH)-positive NSCLC. Addition of trastuzumab to gemcitabine-cisplatin was well tolerated, side-effects were as expected, and trastuzumab did not exacerbate the known toxicity of gemcitabine and cisplatin. Symptomatic cardiotoxicity was observed in one trastuzumab-treated patient. Serum trastuzumab concentrations in the presence of gemcitabine-cisplatin were comparable to those of trastuzumab alone. CONCLUSIONS: Trastuzumab plus gemcitabine-cisplatin is well tolerated. Clinical benefit was not observed. Although HER2 3+/FISH-positive patients may benefit from trastuzumab, the subgroup is too small to provide definitive information. No significant effect of gemcitabine-cisplatin on trastuzumab pharmacokinetics was observed.