吉西他滨联合顺铂与去甲长春碱联合顺铂治疗晚期非小细胞肺癌的临床研究

目的 观察比较吉西他滨联合顺铂(GC方案)与去甲长春碱联合顺铂(VC方案)治疗晚期非小细胞肺癌的疗效、生存率及毒副反应。方法 对67例经病理或细胞学证实的晚期非小细胞肺癌患者给予联合化疗，GC方案32例，VC方案35例，两组病例具有可比性。吉西他滨1000～1250mg／m^2，静脉滴注第1、8天，顺铂80～100mg／m^2，静脉滴注第1～3天，去甲长春碱25mg／m^2，静脉滴注第1、8天，21天为一个周期，每例患者治疗2周期以上。结果 GC组总有效率37．5％，1年生存率38．7％，中位生存期9．5个月；VC组总有效率34．3％，1年生存率34．3％，中位生存期8．6个月。两组间有效率、1年生存率比较差异均无显著性(P=0．59，P=0．48)。最常见的毒副反应为骨髓抑制，GC组Ⅲ～Ⅳ度血小板减少发生率显著高于VC组(P=0．015)，而VC组Ⅲ～Ⅳ度白细胞减少发生率显著高于GC组(P=0．01)。结论 吉西他滨联合顺铂和去甲长春碱联合顺铂治疗NSCLC，疗效肯定，毒性均可耐受。两方案疗效无显著性差异。     

吉西他滨联合顺铂与联合多西紫杉醇治疗非小细胞肺癌的随机对照研究

目的含铂类方案目前是治疗晚期非小细胞肺癌（NSCLC）的标准方案，但其严重的毒副反应促使人们寻找新的替代方案，本研究探讨用吉西他滨联合多西紫杉醇与吉西他滨联合顺铂方案治疗晚期NSCLC的疗效、生存率及毒副反应。方法对62例经病理或细胞学证实的晚期NSCLC的初治患者给予联合化疗，随机分为GT（吉西他滨联合多西紫杉醇）组与GP（吉西他滨联合顺铂）组，两组病例具有可比性，GT组31例，吉西他滨1000mg／m^2，静脉滴注，d1,8，多西紫杉醇（艾素）75mg／m^2加入生理盐水200mL中静脉滴注1h，d1；GP组31例，吉西他滨1000mg／m^2，静脉滴注，d1,8，顺铂25mg/m^2，静脉滴注，d1-3，21d为1个周期，每例治疗不超过6个周期。结果GT组患者总有效率为35．4％，1年生存率为76．2％，中位生存期18．6个月，中位TTP4．9个月，中位PFS3．0个月；GP组患者总有效率为32．2％，1年生存率为67．8％，中位生存期为14．6个月，中位4．4个月，中位PFS3．0个月。两组间有效率、1年生存率、中位生存期差异无统计学意义。最常见的毒副反应为恶心呕吐，GT和GP组的Ⅲ＋Ⅳ度反应发生率分别为3．2％和54．8％，差异有统计学意义（P〈0．05），其余毒副反应轻微，可耐受。结论吉西他滨联合多西紫杉醇与吉西他滨联合顺铂相比疗效相似，但毒副反应轻，安全可行，耐受性好，中位生存期、1年生存率及生活质量以吉西他滨联合多西紫杉醇的非铂方案较好，值得临床推荐应用。     

吉西他滨联合顺铂与吉西他滨联合诺维本治疗晚期非小细胞肺癌的临床研究

背景与目的:含铂联合方案虽然已成为治疗非小细胞肺癌的标准方案,但其严重的毒副反应促使人们寻找新的代替方案.本研究拟观察比较吉西他滨联合顺铂(GP方案)与吉西他滨联合诺维本(GN方案)治疗晚期非小细胞肺癌的疗效,生存率及毒副反应.方法:对82例经病理或细胞学证实的晚期非小细胞肺癌的初治或手术、放疗后患者给予联合化疗,随机分为GP组或GN组.GP方案组42例,GN方案组40例,两组病例具有可比性.GP组吉西他滨1000 mg/m2,静脉滴注,d1、8,顺铂80 mg/m2,静脉滴注d1,GN组吉西他滨1 000 mg/m2静脉滴注,d1、8,诺维本25 mg/m2,静脉推注d1、8.21天为1个疗程.每例病人治疗2个疗程以上.结果:GP组总有效率(PR+CR)为28.6%,1年生存率为64%,中位生存期8.78个月;GN组总有效率(PR+CR)25%,1年生存率66%,中位生存期9.87个月.两组间有效率、1年生存率比较差异无显著性.最常见的毒副反应为恶心,呕吐,GP组和GN组的3～4度反应发生率分别为52.38%和2.5%,差别有统计学意义(P=0.0005).其余毒副反应轻微,可耐受.结论:吉西他滨联合顺铂与吉西他滨联合诺维本相比,疗效相似,非铂类方案的毒副反应小于含铂类方案.     

吉西他滨联合顺铂与去甲长春碱联合顺铂治疗老年晚期非小细胞肺癌临床分析

目的观察比较吉西他滨联合顺铂(GP方案)与去甲长春碱联合顺铂(NP方案)治疗老年晚期非小细胞肺癌的疗效、生存期及毒副反应.方法对61例经病理或细胞学证实的晚期非小细胞肺癌老年患者(年龄＞70岁)随机分为两组,GP方案组30例,NP方案组31例.GP组:吉西他滨1000 mg/m2,静脉滴注,第1,8天;顺铂80～100 mg/m2,静脉滴注,第1天.NP组:去甲长春碱25 mg/m2,静脉滴注,第1,8天;顺铂用法及剂量同GP组.两组均21 d为一周期,每例患者治疗两周期以上.结果 GP组总有效率40.0%,1年生存率为34.8%,中位生存期9.3个月;NP组总有效率38.7%,1年生存率30.0%,中位生存期为8.8个月.两组间总有效率、1年生存率比较差异均无显著性(P=0.58,P=0.51).最常见的毒副反应为骨髓抑制,GP组Ⅲ～Ⅳ度血小板减少发生率显著高于NP组(P=0.016),而NP组Ⅲ～Ⅳ度白细胞减少发生率显著高于GP组(P=0.01).结论吉西他滨联合顺铂与去甲长春碱联合顺铂治疗老年晚期非小细胞肺癌疗效肯定,毒性均可耐受.两方案疗效差异无显著性.     

吉西他滨联合奥沙利铂或顺铂治疗老年人晚期非小细胞肺癌的随机对照临床研究

背景与目的化疗可延长患者生存期，改善生活质量，是治疗晚期非小细胞肺癌的主要方法。对于70岁及以上的老年晚期非小细胞肺癌患者，治疗的毒副反应和治疗耐受性尤其重要。本研究的目的是观察比较吉西他滨联合奥沙利铂和吉西他滨联合顺铂治疗70岁及以上老年人晚期非小细胞肺癌的疗效和毒副反应。方法42例患者按随机表法分为GO组20例（吉西他滨1000mg／m^2，第1、8天；奥沙利铂65mg／m^2，第1、8天）和GP组22例（吉西他滨1000mg／m^2，第1、8天；顺铂30mg／m^2，第1～3天），28天为一周期，均治疗2周期以上。结果GO组CR1例，PR10例，SD7例，PD2例，有效率为55．0％；中位生存期为11．2月，1年生存率为45％。GP组PR9例，SD10例，PD3例，有效率为40．9％；中位生存期为11．8月，1年生存率为50％。两组有效率、中位生存期和1年生存率比较均无显著性差异（P均〉0．05）。毒副反应以白细胞降低和胃肠道反应为主，GP组Ⅲ＋Ⅳ度白细胞下降发生率和恶心呕吐发生率均显著高于GO组（17．4％VS4．8％，20．7％VS3．6％，P均〈0．05），GP组Ⅰ＋Ⅱ度脱发和肾功能异常发生率均显著高于GO组（43．5％ vs 10．7％，14．1％ vs 2．4％，P均〈0．05）。结论对于70岁及以上老年人晚期非小细胞肺癌，吉西他滨加奥沙利铂方案有较好的近期疗效，毒副反应轻，治疗耐受性好，临床应用更安全。     

吉西他滨联合铂类化疗药物治疗晚期非小细胞肺癌临床观察

目的评价吉西他滨联合铂类化疗药物治疗晚期非小细胞肺癌（NSCLC）的临床疗效与毒副反应。方法51例晚期NSCLC患者接受吉西他滨与铂类联合化疗：吉西他滨1000mg／m^2,第1天和第8天;顺铂25mg／m^2,第1-3天或卡铂AUC=5第1天;21天为1个周期。结果完全缓解3例,部分缓解20例,有效率45．1％。中位疾病进展时间5．2个月,中位生存期10．1个月,1年生存率39．2％。主要毒副反应为血液学毒性,恶心呕吐等。结论吉西他滨联合铂类化疗药物是治疗晚期NSCLC安全、有效的联合化疗方案,值得临床进一步研究。     

吉西他滨联合奈达铂与吉西他滨联合顺铂治疗老年晚期非小细胞肺癌的临床研究

目的：评估吉西他滨联合奈达铂与吉西他滨联合顺铂治疗老年晚期非小细胞肺癌（NSCLC）的临床疗效和不良反应。方法：经病理学或细胞学确诊的晚期非小细胞肺癌患者90例,随机分为两组,每组各45例。GN组：吉西他滨（Gem）800mg/m^2,第1、8、15天静注,静脉滴注30分钟,奈达铂（NDP）80-100mg/m^2,静滴,第1天,滴注时间不少于1小时,每3周重复;GP组：吉西他滨（Gem）800mg/m^2,第1、8、15天静注,静脉滴注30分钟,顺铂（DDP）25mg/m^2,静滴,第1-3天,每28天为一个周期。治疗2周期评价疗效,每周期评价不良反应。结果：两组有效率分别为37.8%和40.0%,疾病控制率分别为77.8%和80.0%,中位生存期分别为8.8个月和9.0个月,差异均无显著性（P〉0.05）。GN方案组骨髓抑制尤其是血小板减少略高于GP方案组,但无显著性差异（P〉0.05）;GN方案组消化道反应为35.6%,GP方案组为84.4%,有显著性差异（P〈0.05）。结论：GN和GP方案均为治疗老年晚期NSCLC的有效方案,两方案疗效、疾病控制率及中位生存期均相近,但GN方案消化道反应较GP方案明显较轻,GN方案组患者耐受性更好。     

吉西他滨/卡铂和吉西他滨/顺铂方案治疗晚期非小细胞肺癌的疗效比较

目的 观察吉西他滨／卡铂（GCarb）和吉西他滨／顺铂（GCis）治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 经病理和细胞学证实的40例晚期NSCLC患者随机分为两组。GCarb组给予吉西他滨1000mg/m^2静脉滴注，第1、8天；卡铂AUC4－6静脉滴注，第1天。GCis组给予吉西他滨1000mg/m^2静脉滴注，第1、8天，顺铂30－40mg/m^2静脉滴注，第1－3天。两组均21天为一周期，连续使用2－3周期评价疗效和毒副反应。结果 GCarb组有效率为65％，GCis组为60％，两组疗效无显著性差异（P＞0.5）。两组毒副反应依次为骨髓抑制、胃肠道反应、脱发和皮疹。GCarb组胃肠道反应低于GCis组（P＜0.05）。结论 GCarb和GCis均可作为NSCLC的一线治疗方案。     

国产吉西他滨联合顺铂方案治疗晚期非小细胞肺癌临床观察

目的观察国产吉西他滨（泽菲）联合顺铂方案治疗晚期非小细胞肺癌的疗效与毒副反应。方法共36例接受下述联合方案化疗至少2周期。泽菲1000～1250mg／m^2，d1,8；顺铂25～30mg／m^2，d1-3，21d为1周期。每化疗2周期后评价疗效。每周期化疗结束后均填写药物毒性观察表。结果总有效率为38．9％，初治患者有效率为50．0％，复治患者有效率为25．0％，初治与复治患者疗效差异有统计学意义。骨髓抑制为GP方案主要的毒副反应，以血小板减少为主，有69．4％患者出现血小板减少（Ⅲ度以上占28．9％）。结论国产吉西他滨联合顺铂方案治疗晚期非小细胞肺癌疗效佳、毒副反应小。血小板减少为限制吉西他滨按时继续用药的主要原因。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌30例临床分析

目的观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法采用吉西他滨1000mg／m^2，静脉滴注，第1，8天；顺铂20mg／m^2，静脉滴注，第2～5天；3～4周为1周期，2周期后评价疗效及毒副反应。结果30例中完全缓解1例(3.3％)，部分缓解9例(30％)，总有效率33．3％，毒副反应主要为血小板减少.     

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.     

Comparative Study of Gemcitabine Plus Cisplatin and Gemcitabine Plus Fluorouracil in the Treatment of Advanced Pancreatic Cancer

Objective To compare the efficacy and toxicity of gemcitabine plus cisplatin and gemcitabine plus fluorouracil in the treatment of advanced pancreatic cancer. Methods Sixty patients with advanced pancreatic cancer were randomly divided into a GP group (gemcitabine + cisplatin, 30 cases) and a GF group (gemcitabine + fluorouracil, 30 cases). All patients were treated with gemcitabine at a dose of 1,000mg/m² (diluted in 100ml saline solution over 30 min) once a week for 3 consecutive weeks. The GP Group was followed by 40mg cisplatin via intravenous drip on days 15,16,17. Group GF was followed by 500mg/m²5-Fu (diluted in 5% glucose-saline (GS) 500ml, intravenously, over 6 hr) every day for five subsequent days. Results In the GP group, eight cases (32.0%) were PR and MR, the median survival time was 8.7 months, the Clinical Beneficial Rate (CBR) was 57.7%, and the CA19-9 decreased by over 50% in 13 cases (48.1%). In the GF group, 11 cases (45.8%) were PR and MR, the survival time was 10.1 months, the CBR was 82.1%, and CA19-9 decreased by over 50% in 15 cases(53.6%). There was a significant difference in the CBR between the two groups (P<0.05). The main toxicities in both groups were leucopenia and thrombocytopenia with no significant difference. Conclusions The treatment given to either the GP or GF group is a feasible and well-tolerated chemotherapy regimen for treating advanced pancreatic cancer with improved therapeutic efficacy and few side effects. The median survival period is long and the CBR is high, especially with the GF regimen.     

Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer.

PURPOSE: To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m(2) intravenously weekly x 7 for 8 weeks, then weekly x 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. RESULTS: Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P =.75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade > or = 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. CONCLUSION: The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.     

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。     

吉西他滨联合卡铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌的比较

目的 观察比较健择联合卡铂(GC方案)与健择联合顺铂(GP方案)治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应.方法 81例晚期NSCLC患者随机分成GC方案组(40例)和GP方案组(41例).每例至少治疗2周期.结果 GC和GP组的有效率分别为37.5%和41.5%(P>0.05).中位疾病进展期为4.8个月和5.1个月(P>0.05),中位生存期为8.8个月和9.0个月(P>0.05),1年生存率为40.0%和41.5%(P>0.05).不良反应为骨髓抑制,胃肠道反应,脱发和皮疹.Ⅲ+Ⅳ度白细胞及血小板下降,两组无显著性差异(P>0.05),恶心、呕吐在GP组较GC组表现更为显著(P<0.05).结论 GC方案与GP方案治疗晚期NSCLC疗效相近,GC方案有更好的耐受性,可能对老年,体力状况差患者更为适用.     

Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors

Purpose

Dovitinib is a small molecule kinase inhibitor with activity against the fibroblast growth factor and vascular endothelial growth factor receptor families. The purpose of this phase Ib study was to define the recommended phase 2 dose of the combinations of gemcitabine and cisplatin or gemcitabine and carboplatin plus dovitinib.

Methods

Patients with advanced solid tumors were enrolled in two parallel dose escalation arms (cisplatin- or carboplatin-based regimens). Treatment was administered with gemcitabine (1,000 mg/m² on days 1 and 8), cisplatin (70 mg/m²), or carboplatin (AUC 5) on day 1, and dovitinib (orally on days 1–5, 8–12, and 15–19), every 21 days. The starting dose of dovitinib was 300 mg and was dose escalated in successive cohorts using 3 + 3 dose escalation rules.

Results

Fourteen patients with advanced solid tumors were enrolled, five to the cisplatin arm and nine to the carboplatin arm. Patients enrolled in the cisplatin arm received a median of two cycles of treatment (range 1–5), and patients enrolled in the carboplatin arm received a median of one cycle of treatment (range 1–4). There were no protocol-defined dose-limiting toxicities in the cisplatin arm. However, the cohort was closed due to the need for frequent dose delays and/or reductions and two patients experiencing severe thromboembolic events. There were two dose-limiting toxicities in the carboplatin arm at the starting dose level of dovitinib (both prolonged neutropenia), and the dose of dovitinib was de-escalated to 200 mg. Two additional dose-limiting toxicities (prolonged neutropenia and febrile neutropenia) occurred in the lower dose cohort, and the study was closed. No patients achieved an objective response to treatment.

Conclusions

Dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin was poorly tolerated due to myelosuppression.