吉西他滨单药化疗与联合化疗治疗进展期胰腺癌的疗效观察

目的观察比较吉西他滨单药与联合化疗治疗进展期胰腺癌的疗效。方法回顾性分析了大连医科大学附属一院2002年至2009年收治的45例进展期胰腺癌患者的临床资料,吉西他滨单药组17例,剂量为1000mg/m2,d1、8,三周为一周期;吉西他滨联合治疗组28例,联合化疗方案包括吉西他滨1000mg/m2,d1、8,分别联合：（1）氟尿嘧啶425～600mg/m2,静滴或持续静脉泵入,d1～5;（2）顺铂60～75mg/m2,分3～4d静脉滴入;（3）奥沙利铂85～130mg/m2,d1,静脉滴入;（4）卡培他滨1000mg/m2,每天两次口服,d1～14。21d为一周期。采用Kaplan-Meier生存曲线分析患者的生存期,并比较两组间的临床受益率、中位疾病进展时间、中位生存时间及不良反应。结果吉西他滨联合组及单药组的临床收益率均得到提高,但两组间比较临床受益率、疾病控制率、中位生存时间均无统计学意义。结论吉西他滨联合化疗方案与吉西他滨单药治疗进展期胰腺癌相比,疗效、临床受益率、中位生存期均相似。     

吉西他滨单药或与顺铂联合治疗胰腺癌的临床疗效评价

目的 评价吉西他滨单药以及与顺铂联合治疗局部晚期或转移性胰腺炎的疗效。临床受益反应,生存时间和毒性反应。方法 42例患者随机分为吉西他滨单药组（A组20例）和吉西他滨 顺铂联合组（B组22例）,A组;吉西他滨1000mg/m^2,每周1次,连用7周,休息1周;随后相同剂量每周1次,连用3周,休息1周,B组;吉西他滨1000mg/m^2,每周1次,连用3周,顺铂60mg/m^2,第15天给药,休息1周,每4周重复,边境用药3个周期。结果 42例患者中,可评价客观疗效者34例（A组16例,B组18例,可评价临床受益反应（CBR）者36例（A组16例,B组20例）,可进行毒性反应评估者40例（A组19例,B组21例）,A组：PR1例（6.3%)。MR4例（25.0%),SD7例（43.8%)。PD4例（25.0%)。B组;PR2例（11.0%)。MR3例（16.7%),SD8例（44.4%),PD5例（27.8%)。PR MR SD率A组为75.0%。B组为72.2%。CBR有效率A组为87.5%(14/16),B组为70.0%(14/20)。两组3个月生存率均为100%,6个月生存率分别为81.3%和61.6%。12个月生存率分别为31.3%和11.1%。B组Ⅲ、Ⅳ度血液学毒性反应发生率略高于A组,两组相比,差异无显著性。结论 吉西他滨单药以及与顺铂联合一线治疗局部晚期或转移性胰腺癌有一定的客观疗效。可明显改善患者的生活质量。延长了生存时间,患者耐受良好。     

吉西他滨联合奥沙利铂治疗晚期胰腺癌疗效观察

目的:观察GEMOX联合方案治疗晚期胰腺癌的疗效和毒副反应。方法:19例确诊晚期胰腺癌患者接受至少2个周期的GEMOX联合方案化疗,吉西他滨1000mg/m2,静脉滴入,d1、d8;奥沙利铂130mg/m2,静脉滴入,d1。每21d重复。结果:1例CR,5例PR,8例SD,5例PD,总有效率为31.6%(6/19),毒副反应可以耐受,没有化疗相关的死亡。结论:吉西他滨加奥沙利铂联合化疗是治疗晚期胰腺癌安全有效的方案,可以使部分患者得到临床受益。但需要有Ⅲ期的随机临床试验与吉西他滨单药化疗进行比较,以明确此联合方案的优势。     

晚期胰腺癌的化疗

单药吉西他滨是晚期胰腺癌的标准治疗,但疗效并不理想.吉西他滨已与多种细胞毒药物或生物靶向药物组成多个联合方案,但是在大多数Ⅲ期临床研究中这些联合方案对生存时间的延长并没有超过吉西他滨单药.有Ⅲ期临床研究结果显示埃罗替尼联合吉西他滨可延长晚期胰腺癌患者的生存时间.非吉西他滨的化疗方案也正在评估中,并已初步看到了希望.     

吉西他滨治疗14例晚期胰腺癌

目的：研究吉西他滨（gemcitabine)治疗晚期胰腺癌的疗效。方法：14例进行展期胰腺癌患者,用吉西他滨第1周800mg/m^2,第2周1000mg/m^2,第3周1200mg/m^2,每周1次,每次以0．9％生理盐水100ml溶解后静脉滴注,30分钟滴完,连续3周,随后休息1周为一疗程。以后每4周重复一次,共6个疗程。结果：疼痛缓解有效率为64％（9／14）,处长了中位生存期,平均为8．7个月。临床受益反应为43％。吉西他滨治疗晚期胰腺癌能显著改善晚期胰腺癌患者的临床症状,减轻疼痛。生活质量有明显提高。结论：吉西他滨可作为晚期胰腺癌综合治疗时首选的化疗药物。     

三维适形放疗联合卡培他滨或吉西他滨治疗43例局部晚期胰腺癌

[目的]观察三维适形放疗联合卡培他滨或吉西他滨治疗局部晚期胰腺癌的疗效及毒副反应。[方法]43例局部晚期胰腺癌患者非随机分为两组。A组：卡培他滨800mg/m2,2次/d,每周1~5d口服,联合同期三维适形放疗（DT45~50.4Gy/25~28次,1次/d,5次/周）;B组：吉西他滨每周600mg/m2,每周1次,联合三维适形放疗（同A组）。观察两组的有效率、临床获益及毒副反应。[结果]A、B组有效率（37.5%vs42.1%）、临床获益率（75.0%vs73.6%）、中位生存时间（9.2个月vs10.7个月）、中位无进展生存时间（7.1个月vs7.9个月）以及1年生存率（33.3%vs36.8%）、2年生存率（8.3%vs10.5%）均无统计学差异。吉西他滨组骨髓抑制发生率明显高于卡培他滨组（P〈0.05）,虽然腹泻发生率在卡培他滨组明显更高,但均为Ⅰ/Ⅱ级,患者可耐受。[结论]卡培他滨联合同步放疗可取得较好的临床疗效,患者耐受性良好,其效果尚需临床进一步研究。     

吉西他滨单药治疗老年晚期非小细胞肺癌的临床观察

目的观察吉西他滨单药周剂量治疗老年晚期非小细胞肺癌的疗效和不良反应。方法对45例老年晚期非小细胞肺癌患者(年龄≥65岁)应用吉西他滨800¹000 mg/m2,第1、8天,31000 mg/m2,第1、8天,3⁴周为1个周期,至少治疗2个周期评价疗效和不良反应。结果全组总有效率为26.7%(12/45),临床受益率为71.1%(32/45),无疾病进展生存时间为4.2个月,中位生存时间为8.3个月,1年生存率为31.1%(14/45),主要不良反应为骨髓抑制、胃肠道反应、皮疹和肝肾功能受损。结论吉西他滨单药周剂量治疗老年晚期非小细胞肺癌耐受性较好,生活质量较高。     

吉西他滨联合顺铂在进展期胰腺癌动脉灌注化疗中的应用

目的评价吉西他滨(商品名健择)联合顺铂动脉灌注治疗进展期胰腺癌的疗效和毒副反应.方法对21例进展期胰腺癌患者采用吉西他滨联合顺铂动脉灌注化疗,治疗间隔时间为3周,随访观察患者临床受益反应、肿瘤情况、毒副作用及生存时间.结果21例患者的临床受益率为42.9%,客观缓解率为19.1%,中位疾病进展时间为4.2个月,中位生存时间为9.2个月.毒副反应较常见,但多为WHOⅠ～Ⅱ级.结论经动脉灌注吉西他滨和顺铂治疗进展期胰腺癌可获得较好的临床受益反应,无严重毒副反应.     

康莱特联合吉西他滨治疗进展期胰腺癌的疗效观察

目的：观察康莱特联合吉西他滨治疗进展期胰腺癌的临床疗效、临床获益反应和不良反应.方法：40例未接受过全身化疗的进展期胰腺癌患者,至少接受2个周期的康莱特联合吉西他滨化疗方案.康莱特200ml静滴,每天1次,吉西他滨1000mg/m2,第1天和第8天,每21天为一个周期.结果：40例患者中3例临床缓解,13例部分缓解,11例稳定.总的疾病控制率为67.5％.疼痛缓解率为88.6％.骨髓抑制发生率为37.5％.无化疗相关死亡.结论：康莱特联合吉西他滨治疗进展期胰腺癌可提高疾病控制率,改善患者生活质量,减轻疼痛,减少不良反应的发生.     

吉西他滨联合同步放疗治疗局部晚期胰腺癌疗效观察

 目的 评价立体定向放射治疗联合吉西他滨与吉西他滨单药治疗局部晚期胰腺癌的疗效.方法 治疗组56例胰腺癌行立体定向放疗联合吉西他滨单药化疗。对照组50例仅行吉西他滨单药化疗。立体定向放疗,总剂量4 000～4 500 cGy, 10次分割。同步化疗方案为吉西他滨500 mg/m² 第1、8天。对照组给予输注吉西他滨1 000 mg/m², 第1、8、15天结果治疗结束2个月后CT复查,治疗组及对照组有效率分别为82%、16%,疼痛缓解率分别为 67%、17%。疾病进展时间治疗组为14个月,优于对照组7.5个月,差异有统计学意义（χ²= 7.31,P=0.032）。中位生存期治疗组和对照组分别为15.8个月及13.2个月,差异无统计学意义（χ²= 3.28,P=0.082）。结论立体定向放射治疗联合吉西他滨治疗局部晚期胰腺癌较单纯化疗组有效率、疼痛缓解率高;能延长疾病进展时间,但未能改善总生存期。     

吉西他滨联合奥沙利铂治疗晚期胰腺癌患者的疗效

背景与目的:吉西他滨是目前治疗晚期胰腺癌的最有效的药物之一,初步的研究显示,与奥沙利铂联合(GEMOX)的疗效优于吉西他滨单药,但国内使用GEMOX方案治疗胰腺癌的研究报道并不多.本研究目的是观察GEMOX方案治疗晚期胰腺癌患者的有效率、生存期和毒副反应,为临床治疗提供指导.方法:本研究为单中心、回顾性临床分析.选择32例未接受过化疗的初治Ⅲ～Ⅳ期胰腺癌患者,所有患者均至少接受2个周期的GEMOX方案(吉西他滨1000 mg/m2,静脉滴入,d1、d8;奥沙利铂85～130 mg/m2,静脉滴入,d1;每21 d重复)化疗.结果:28例患者可评价疗效,8例部分缓解(partial remission,PR),8例病情稳定(stable disease,SD),12例病情进展(progressive disease,PD),4例不能评估(not assessable,NA),总有效率为25.0%,临床获益率46.9%(15例),中位无进展生存期(progression-free survival,PFS)为4.7个月,中位生存期8.6个月,1年生存率为32.6%.骨髓抑制的总发生率为70.9%,其中Ⅲ、Ⅳ度的发生率为32.3%(白细胞下降的发生率为19.4%,血红蛋白下降的发生率为12.9%,血小板下降的发生率为22.6%).恶心、呕吐和腹泻的发生率为56.2%,其中Ⅲ度呕吐2例.肝功能异常的总发生率为25.0%,全部为Ⅰ、Ⅱ度.外周神经毒性发生率为43.8%,全部为Ⅰ度.无化疗相关的死亡.结论:GEMOX方案是治疗晚期胰腺癌的有效方案,总体临床耐受性良好,其主要的不良反应为骨髓抑制.     

Phase I/II study of combination chemotherapy with gemcitabine and UFT for advanced pancreatic cancer in a multi-center trial

The aim of this phase I/II study was to evaluate the tolerability and efficacy of combination chemotherapy with gemcitabine (GEM) and UFT for advanced pancreatic cancer. In phase I study UFT was given orally every day for 14 days and GEM was infused on day 1 and 8 at three dose levels (800, 900, 1,000 mg/m(2)/week) every 21 days. GEM 1,000 mg/m(2) and UFT 400 mg/m(2) did not reach the maximum tolerated dose. We decided that the recommended dose (RD) was GEM 1,000 mg/m(2)and UFT 400 mg/m(2). In phase II study 27 patients were enrolled and received GEM and UFT at RD. The tumor response rate was 17.6%, and the median survival was 221 days, which was very similar to that of GEM monotherapy. Due to adverse events, especially liver dysfunction, protocol therapy was discontinued in 12 patients. This study could not revealed the superiority of the GEM monotherapy.     

吉西他滨联合顺铂或氟尿嘧啶治疗晚期胰腺癌临床疗效的比较

目的　比较GP方案 (吉西他滨 顺铂 )与GF方案 (吉西他滨 氟尿嘧啶 )治疗晚期胰腺癌的近期疗效和毒副作用。方法　经病理组织学或细胞学检查证实的 60例胰腺癌患者 ,随机分为GP组和GF组 ,各 3 0例。GP组给予吉西他滨 10 0 0mg/m2加生理盐水 10 0ml,静脉滴注 3 0min ,第 1、8、15天 ;顺铂 40mg ,静脉滴注 ,第 15、16、17天。GF组给予吉西他滨 10 0 0mg/m2 加生理盐水 10 0ml ,静脉点滴 3 0min ,第 1、8、15天 ;氟尿嘧啶 5 0 0mg/m2 加 5 %GS 5 0 0ml ,静脉滴注时间超过 6h ,第 1～ 5天。结果　GP组PR 3例 ,MR 5例 ,NC 12例 ,PD 5例 ,PR MR为 3 2 .0 % ,中位生存期为 8.7个月 ,临床受益反应率 (CBR )为 5 7.7% (15 /2 6) ,CA 19 9水平下降超过 5 0 %者达 48.1% (13 /2 7)。GF组PR 3例 ,MR 8例 ,NC 9例 ,PD 4例 ,PR MR为 45 .8% ,中位生存期为 10 .1个月 ,CBR 82 .1% (2 3 /2 8) ,CA19 9水平下降超过 5 0 %者达 5 3 .6% (15 /2 8)。 2组比较 ,CBR有显著性差异 (P <0 .0 5 ) ,GF疗效较佳。不良反应主要为白细胞减少和血小板减少 ,2组无显著性差异。结论　含吉西他滨的联合化疗方案与以往单药方案比较 ,疗效高、副作用小、患者中位生存期长 ,临床受益反应率 (CBR )高 ;GP方案和GF方案比较 ,后者CBR更高 (5     

Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil,a randomized controlled study

PURPOSE: To determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy (CCRT) vs. 5-fluorouracil (5-FU) CCRT for locally advanced pancreatic cancer. METHODS AND MATERIALS: Thirty-four patients with locally advanced pancreatic cancer were studied. Eighteen patients were randomized to receive GEM CCRT (600 mg/m(2)/wk for 6 weeks) and 16 patients to receive bolus 5-FU CCRT (500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks). All patients were to receive 3D-CRT 50.4-61.2 Gy at 1.8-Gy/d fractions and GEM (1000 mg/m(2) weekly for 3 weeks repeated every 4 weeks) after RT. RESULTS: The median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group (p = 0.027 and p = 0.019, respectively). The quality-adjusted life month survival time was 11.2 +/- 0.5 months for GEM CCRT and 6.0 +/- 0.3 months for 5-FU CCRT patients (p <0.001). The response rate was 50% (four complete responses and five partial responses) for GEM CCRT and 13% (two partial responses) for 5-FU CCRT (p = 0.005). Pain control was 39% for GEM CCRT and 6% for 5-FU CCRT (p = 0.043). Grade 3-4 neutropenia (34% vs. 19%), thrombocytopenia (0% vs. 7%), nausea (33% vs. 31%), vomiting (17% vs. 19%), hospitalization days per month of survival (7.4 +/- 1.7 days vs. 8.0 +/- 1.3 days), and full dose of RT received (78% vs. 75%) were not significantly different between the GEM CCRT and 5-FU CCRT patients. CONCLUSION: GEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability.     

Phase I and pharmacokinetic study of imatinib mesylate (Gleevec) and gemcitabine in patients with refractory solid tumors.

PURPOSE: Preclinical data shows improvements in response for the combination of imatinib mesylate (IM, Gleevec) and gemcitabine (GEM) therapy compared with GEM alone. Our goals were to determine the maximum tolerated dose of GEM and IM in combination, the pharmacokinetics of GEM in the absence and in the presence of IM, and IM pharmacokinetics in this combination. Patients and Methods: Patients with refractory malignancy, intact intestinal absorption, measurable/evaluable disease, adequate organ function, Eastern Cooperative Oncology Group PS 0-2, and signed informed consent were eligible. Initially, treatment consisted of 600 mg/m2 of GEM (10 mg/m2/min) on days 1, 8, and 15, and 300 mg of IM daily every 28 days. Due to excessive toxicity, the schedule was altered to IM on days 1 to 5 and 8 to 12, and GEM on days 3 and 10 every 21 days. Two final cohorts received IM on days 1 to 5, 8 to 12, and 15 to 19. RESULTS: Fifty-four patients were treated. IM and GEM given daily at 500 to 600 mg/m2 on days 1, 8, and 15 produced frequent dose-limiting toxicities. With the modified scheduling, GEM given at 1,500 mg/m2/150 min was deliverable, along with 400 mg of IM, without dose-limiting toxicities. Three partial (laryngeal, renal, and mesothelioma) and two minor (renal and pancreatic) responses were noted at GEM doses of 450 to 1,500 mg/m2. Stable disease >24 weeks was seen in 17 patients. CA19-9 in 7 of 10 patients with pancreatic cancer was reduced by approximately 90%. IM did not significantly alter GEM pharmacokinetics. CONCLUSION: The addition of intermittently dosed IM to GEM at low to full dose was associated with broad antitumor activity and little increase in toxicity.     

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged >70 years with ECOG performance status (PS)< or =2, or younger with PS=2, were randomly treated with: GEM 1200 mg m(-2) on days 1, 8 and 15 every 28 days; PTX 100 mg m(-2) on days 1, 8 and 15 every 28 days; GEM 1000 mg m(-2) plus PTX 80 mg m(-2) (GT) on days 1 and 8 every 21 days; GEM 1000 mg m(-2) plus VNR 25 mg m(-2) (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade > or =2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS< or =1 (hazard ratio (HR)=0.67; 95% CI 0.51-0.90), and doublet treatments (HR=0.76; 95% CI 0.59-0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PS< or =1.     

Phase II study on low dose gemcitabine plus oral chemotherapy with uracil-tegafur and cyclophosphamide in combination with radiotherapy against recurrent and advanced pancreatic cancer

The present study assessed the anti-tumor effects and clinical benefits of intravenous (i.v.) or intra-arterial (i.a.) gemcitabine (GEM) at low dose plus oral chemotherapy with uracil-tegafur (UFT) and cyclophosphamide (CPA) in combination with radiotherapy (RT) against recurrent and advanced pancreatic cancers. A total of 22 patients with 15 advanced or 7 recurrent pancreatic cancer were enrolled. The target lesions included 15 primary tumors, 9 liver metastases, 3 local recurrences, 1 lung metastasis and 1 pleural effusion. The patients were each given GEM at 200-400 mg weekly or biweekly, UFT at 300 mg/day daily and CPA at 50 mg/day every other day in combination with RT at a total dose of 40-60 Gy. The primary efficacy measures were the overall response rate (RR) and survival. Furthermore, the clinical benefit response (CBR) was classified by measuring the pain intensity, analgesic consumption, Karnofsky performance status and body weight. The regimen was well tolerated, and the major side effects included anorexia, general malaise and myelo-suppression. In each case, dose reduction was effective in resolving these side effects. The dose limiting side effect was thrombocytopenia. Eleven patients received i.v. GEM alone, 6 patients received i.a. GEM alone and 5 patients received both. The objective responses were evaluated in all patients, and the overall RR was 27% (2 complete responses, 4 partial responses, 6 stable diseases and 10 progressive diseases). A CBR was experienced in 22.7% of the patients. The mean survival period was 10.6 months (2-20 months), and the 1-year survival rate was 42.2%. There were no differences in RR and survival among the different administration methods of GEM. In conclusion, i.v. or i.a. GEM at low dose, UFT and CPA in combination with RT is a well-tolerated regimen with beneficial clinical efficacy, and is worthy of further study.     

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study

PURPOSE: The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit. Gemcitabine (GEM) has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer. We evaluated the feasibility of postoperative administration of GEM alone, followed by concurrent GEM and irradiation (RT) after curative resection for pancreatic adenocarcinoma. METHODS AND MATERIALS: GEM 1000 mg/m(2) on Days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by GEM 300 mg/m(2) weekly +40 Gy in a split course. Twenty-two patients (median age 59 years, range 39-74, Performance Status 0-1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. RESULTS: For GEM alone, all patients received the three planned courses, with dose reductions in 7 (32%) of 22 patients. All patients, except two, completed full chemoradiation; one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia and the other stopped RT after 32 Gy because of early disease progression. No reduction in GEM during RT was necessary; no toxic death was noted; and World Health Organization Grade 3-4 hematologic and nonhematologic toxicities occurred in 8 (36%) and 7 (nausea, vomiting) (32%) of 22 patients respectively. No late toxicity developed. After a median follow-up of 15 months, 11 patients were alive, and 2 patients had died of causes unrelated to their disease or toxicity, The median disease-free survival and overall survival was 6 and 15 months, respectively. CONCLUSION: This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer. Its intensification with continuous RT is currently being investigated.