伊立替康联合顺铂与依托泊苷联合顺铂方案一线治疗广泛期小细胞肺癌的临床疗效观察

目的:比较伊立替康加顺铂(CPT-11+ DDP)及依托泊苷加顺铂(VP-16+ DDP)两种方案一线治疗广泛期小细胞肺癌(ED-SCLC)的临床疗效及毒副反应.方法:初治ED-SCLC患者60例,IP组31例患者,应用DDP 30mg/m2静脉滴注,d1-d3,CPT-11 200mg/m2静脉滴注,d1;EP组29例患者,应用方案DDP30mg/m2静脉滴注,VP-16 80mg/m2静脉滴注,均为d1-d3,两种方案均21d为一个周期,连用4个周期.每两个周期评价疗效及毒副反应.结果:IP组有效率为61.3％,EP组有效率为58.6％,两组比较差异有统计学意义(P＜0.05);IP组无进展生存期6.9个月,EP组无进展生存期4.8个月,两组比较差异无统计学意义(P＞0.05);两组毒副反应发生率比较差异均无统计学意义(P＞0.05).结论:依托泊泔联合顺铂方案比较伊立替康联合顺铂方案疗效相似,但二者的毒性谱不同(IP组的腹泻发生率明显高于EP组,EP方案血液学毒性大),且IP组生存期较长,是ED-SCLC一线治疗的安全有效方案.     

顺铂联合伊立替康或足叶乙甙方案治疗初治广泛期小细胞肺癌的Ⅱ期临床研究

目的探讨伊立替康联合顺铂(IP)方案和足叶乙甙联合顺铂(EP)方案治疗初治广泛期小细胞肺癌的疗效和安全性。方法选取2010年1月至2012年12月间收治的初治广泛期SCLC患者50例,随机分为IP组和EP组,每组各25例,采集两组患者的临床资料。IP组治疗方案:伊立替康65 mg/m2静滴,第1、8天,顺铂75 mg/m2静滴,第1天。EP组治疗方案:足叶乙甙100mg/m2静滴,第1,2,3天,顺铂75mg/m2静滴,第1天。21天为1个周期,至少进行2个周期的化疗后评价客观疗效及不良反应。结果 50例患者评价疗效:IP组CR 2例,PR 17例,SD 3例,客观有效率76.0%,疾病控制率88.0%。EP组无CR病例,PR 17例,SD 1例,客观有效率68.0%,疾病控制率72.0%。两组客观有效率差异无统计学意义(P=0.062);疾病控制率差异有统计学意义(P=0.032),IP组高于EP组。IP组中位无进展生存时间为6.1个月,中位生存时间为17.8月;1年及2年生存率分别为69.7%和25.1%,而EP组中位无进展生存时间为5.9个月,中位生存时间15.2个月,1年及2年生存率分别为58.7%和15.4%,两组比较差异无统计学意义(P>0.05)。患者不良反应主要是血液学毒性和胃肠道反应,IP组腹泻发生率高于EP组,差异有统计学意义(P=0.0067)。结论顺铂联合伊立替康或足叶乙甙方案治疗初治广泛期小细胞肺癌的临床疗效较好,不良反应均可耐受,值得进一步研究。     

伊立替康联合顺铂与紫杉醇联合顺铂治疗难治性小细胞肺癌的临床观察

目的:观察伊立替康联合顺铂(IP组)与紫杉醇联合顺铂(TP组)二线治疗难治性小细胞肺癌的近期疗效及不良反应.方法:共63例患者,均为一线EP方案化疗失败或治疗后3-6个月内复发的小细胞肺癌患者.IP组:伊立替康60mg/m2,第1,8天,顺铂25mg/m2,第1-3天,静脉滴注.TP组:紫杉醇90mg/m2,第1,8天,顺铂25mg/m2,第1-3天,静脉点滴,均为21天1个周期,每2周期评价一次.结果:IP组32例,有效率34.3%(11/32).TP组31例,有效率32.3%(9/31),两组近期疗效无显著性差异(P>0.05).两组中位疾病进展时间(mTTP)为3.0个月与3.2个月.中位生存期(MST)分别为8个月和8.5个月,无显著性差异(P>0.05).两组不良反应:Ⅲ/Ⅳ度粒细胞下降分别为28.1%和35.5%,Ⅲ/Ⅳ度血小板减少分别为9.3%和12.5%(P<0.05),延迟性腹泻IP组高于TP组,分别为23.1%和3.2%,有显著性差异(P﹤0.001).结论:伊立替康联合顺铂与紫杉醇联合顺铂二线治疗难治性小细胞肺癌均取得较好疗效,两方案不良反应均可以耐受.     

奥沙利铂或顺铂联合足叶乙甙治疗老年广泛期小细胞肺癌的随机对照临床研究

背景与目的 足叶乙甙(VP-16)联合顺铂(DDP)是广泛期小细胞肺癌(small cell lung cancer,SCLC)一线联合化疗中最常用的方案,但顺铂的恶心呕吐毒副反应影响患者的生存质量.本研究拟比较足叶乙甙联合奥沙利铂或顺铂一线治疗老年广泛期SCLC的疗效及毒副反应.方法 未经抗肿瘤治疗的老年广泛期SCLC患者71例,随机分成两组,EO组(足叶乙甙80 mg/m2第1-5天+奥沙利铂130 mg/m2第1天静脉滴注,每21天重复)35例,EP组(足叶乙甙80 mg/m2第1-5天+顺铂25 mg/m2第1-3天静脉滴注,每21天重复)36例,至少治疗2周期以后评价疗效及不良反应.结果 EO组与EP组相比,治疗缓解率(55.9％ vs 54.3％,P=0.894),疾病控制率(82.4％ vs 77.1％,P=0.591),中位无进展生存期(5.5个月vs 4.7个月,P=0.638),中位生存时间(10.5个月vs 9.1个月,P=0.862)差异均无统计学意义;毒副反应方面,EO组恶心呕吐等消化道反应发生率低于EP组(65.7％vs 97.2％,P=0.001),但Ⅰ级-Ⅱ级神经毒性发生率高于EP组(74.3％ vs 11.1％,P＜0.001).结论 足叶乙甙联合奥沙利铂或顺铂两种方案用于一线治疗老年广泛期SCLC的疗效相当,但EO组患者耐受性相对较好.     

拓扑替康联合顺铂方案与足叶乙甙联合顺铂方案治疗小细胞肺癌临床对比分析

目的 比较分析拓扑替康联合顺铂(TP)方案与足叶乙甙联合顺铂(EP)方案治疗小细胞肺癌(SCLC)的疗效和毒副反应.方法 入组SCLC 92例,其中47例给予TP方案化疗:拓扑替康0.75～1.00 mg/(m2·d),d1～5;顺铂25 mg/(m2·d),d1～3.45例给予EP方案化疗:足叶乙甙100 mg/(m2·d),d1～5;顺铂25 mg/(m2·d),d1～3.两种方案均以21 d为1周期,治疗2个周期后评价疗效和毒副反应.结果 TP组和EP组中位生存期分别为12个月和7个月(P<0.01),中位疾病进展时间分别为5个月、3个月(P>0.05),有效率分别为59.6%、40.0%(P>0.05).两组主要毒副反应均为骨髓抑制和胃肠道反应,差异无统计学意义(P>0.05).结论 与EP方案相比,TP方案治疗SCLC更能延长患者生存期,且毒副反应亦可耐受.     

伊立替康联合顺铂与紫杉醇联合顺铂二线治疗小细胞肺癌的临床观察

目的:观察伊立替康联合顺铂(IP组)与紫杉醇联合顺铂(TP组)周剂量方案二线治疗复发或进展期小细胞肺癌的疗效及不良反应。方法:共96例EP(依托泊甙联合顺铂)方案或CAV方案(环磷酰胺、表柔比星联合长春新碱)化疗后复发或进展的小细胞肺癌患者,采用信封法随机分组进入IP组49例和TP组47例接受治疗。IP组:伊立替康60mg/m~2,第1,8,15天;顺铂25mg/m~2,第1天～3天,静滴。TP组:紫杉醇60mg/m~2,第1,8,15天;顺铂25mg/m~2,第1天～3天,静滴;均为28天1个周期,每2周期评价一次疗效。结果:IP组49例,有效率36.7%(18/49);TP组47例,有效率34%(16/47),两组近期疗效差异无统计学意义(P>0.05)。两组中位生存期(MST)均为37.0周,差异无统计学意义(P>0.05)。两组毒副作用主要表现为:Ⅲ度～Ⅳ度白细胞减少,TP组高于IP组(34.0%vs 22.4%,P<0.05);Ⅲ度～Ⅳ度血小板减少TP组高于IP组(17.0%vs 10.2%,P<0.05);延迟性腹泻IP组高于TP组(22.4%vs 6.4%,P<0.01)。结论:伊立替康联合顺铂与紫杉醇联合顺铂周剂量方案二线治疗小细胞肺癌近期疗效较好,毒副作用可以耐受,值得进一步研究。     

伊立替康联合顺铂治疗广泛期小细胞肺癌的临床观察

为了观察伊立替康联合顺铂治疗广泛期小细胞肺癌(SCLC)的近期疗效及毒副反应,对28例患者采用伊立替康联合顺铂治疗的方法.伊立替康 60 mg/m2,静脉滴入,d1、d8、d15;顺铂 60 mg/m2 ,静脉滴入,d1.28 d 为1个周期,2个周期后评价疗效. 结果可评价疗效28例,其中CR 6例(21.4%),PR 12例(42.9%),NC 4例(14.3%),PD 6例(21.4%),总有效率为64.3%(18/28).主要毒副反应为腹泻、骨髓抑制、恶心和呕吐.初步结果提示,伊立替康联合顺铂治疗SCLC有明显的疗效,毒副反应可以耐受,可以作为SCLC临床治疗的有效方案之一.     

伊立替康或足叶乙甙联合顺铂方案一线治疗小细胞肺癌的临床随机对照研究

  目的  本研究为比较伊立替康联合顺铂(irinotecan plus cisplatin, IP)方案与足叶乙甙联合顺铂(etoposide plus cisplatin, EP)方案一线治疗小细胞肺癌(SCLC)的近期疗效、远期生存及不良反应。  方法  首都医科大学附属北京胸科医院肿瘤内科从2008年3月至2010年3月收治的60例SCLC患者, 随机分为两组, 分别接受IP和EP方案的治疗。主要研究终点为无进展生存期(progression-freesurvival, PFS), 次要研究终点为总生存(overall survival, OS), 客观反应率(response rate, RR)和不良反应。  结果  60例患者中, 59例可评价疗效, 其中IP组RR 65.4%(19/29), 中位PFS为9.6个月, 中位OS为17.3个月; EP组RR 73.3%(22/30), 中位PFS为9.7个月, 中位OS为17.4个月, 两组比较均无统计学差异(P=0.864;P=0.982;P=0.997)。两组主要不良反应均为骨髓抑制和胃肠道反应, 但Ⅲ+Ⅳ度不良反应均无统计学差异(P > 0.05), IP组腹泻发生率高于EP组(26.6%vs.0), 两组比较差异具有统计学意义(P=0.003)。  结论  IP方案一线治疗SCLC近期疗效及远期生存均与EP方案相当, 且不良反应可耐受。      

伊立替康联合顺铂方案与足叶乙甙联合顺铂方案治疗小细胞肺癌的随机对照临床研究

背景与目的 足叶乙甙＋顺铂（EP）方案是治疗小细胞肺癌（SCLC）的标准方案，本试验拟比较伊立替康＋顺铂（IP）方案与EP方案治疗SCLC的近期疗效和毒副作用。方法 61例SCLC患者被随机分组，接受IP或EP方案化疗2个周期以上，评价疗效及毒副作用。结果 ①IP组有效率为66．7％，完全缓解率为23．3％；EP组有效率为61．3％，完全缓解率为16．1％。两组近期疗效比较无显著性差异（P〉0．05）。②IP组Ⅲ～Ⅳ度白细胞下降2例（6．7％），EP组11例（35．5％），两组比较有显著性差异（P〈0．01）；IP组Ⅲ～Ⅳ度中性粒细胞下降2例（6．7％），EP组16例（51．6％），两组比较有显著性差异（P〈0．001）；IP组血小板减少8例（26．7％），EP组25例（80．6％），两组比较有显著性差异（P〈0．001）；IP组腹泻11例（36．7％），EP组2例（6．5％），两组比较有显著性差异（P〈0．01）；两组Ⅲ～Ⅳ度恶心呕吐比较无显著性差异（P〉0．05）；胆碱能综合征、肝肾功能异常、周围神经炎、脱发、静脉炎等均少见。结论 IP和EP方案是治疗SCLC有效的方案。与EP方案相比，IP方案疗效相似，而血液学毒性较轻，IP方案的腹泻毒性较明显，可以通过对症治疗控制。     

伊立替康或依托泊苷联合顺铂一线治疗广泛期小细胞肺癌的疗效比较

目的 比较伊立替康联合顺铂（irinotecan plus cisplatin,IP）与依托泊苷联合顺铂（etoposide plus cisplatin,EP）两种方案一线治疗广泛期小细胞肺癌（extensive-disease small cell lung cancer,ED-SCLC）的临床疗效和毒副反应。方法 初治ED-SCLC患者50例,予IP方案治疗25例,顺铂（DDP） 30 mg/m²静脉滴注,d1~d3;伊立替康（CPT-11）150 mg/m²静脉滴注,d1;予EP方案治疗25例,DDP 30 mg/m²静脉滴注,d1~d3;依托泊苷（Vp-16）60 mg/m²静脉滴注,d1~d5,两种方案均以21 d为1个周期,连续化疗4个周期,每2个周期评价疗效及毒副反应。结果 IP方案和EP方案有效率分别为72.0％、64.0％,差异无统计学意义（P=0.544）;两种方案血液学毒性发生率的差异无统计学意义（P>0.05）,但IP方案腹泻发生率明显高于EP方案（P=0.002）。结论 伊立替康联合顺铂或依托泊苷联合顺铂一线治疗广泛期小细胞肺癌的疗效相似,患者均可耐受。     

Pilot study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by irinotecan and cisplatin for limited-stage small cell lung cancer: Japan Clinical Oncology Group 9903.

PURPOSE: Irinotecan and cisplatin (IP) significantly improved survival compared with etoposide and cisplatin (EP), in patients with extensive-stage small cell lung cancer (SCLC) in a previous Japan Clinical Oncology Group (JCOG) randomized trial. JCOG9903 was conducted to evaluate the safety of sequentially given IP following concurrent EP plus twice-daily thoracic irradiation (TRT) for the treatment of limited-stage SCLC (LSCLC). EXPERIMENTAL DESIGN: Between October 1999 and July 2000, 31 patients were accrued from 10 institutions. Thirty patients were assessable for toxicity, response, and survival. Treatment consisted of etoposide 100 mg/m(2) on days 1 to 3, cisplatin 80 mg/m(2) on day 1, and concurrent twice-daily TRT of 45 Gy beginning on day 2. The IP regimen started on day 29 and consisted of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1, with three 28-day cycles. RESULTS: There were no treatment-related deaths. The response rate was 97% (complete response, 37%; partial response, 60%). Median overall survival was 20.2 months; 1-, 2-, and 3-year survival rates were 76%, 41%, and 38%, respectively. Of the 24 patients who started the IP regimen, 22 received two or more cycles. Hematologic toxicities of grade 3 or 4 included neutropenia (67%), anemia (50%), and thrombocytopenia (4%). Nonhematologic toxicities of grade 3 or 4 included diarrhea (8%), vomiting (8%), and febrile neutropenia (8%). Of the 20 patients with recurrence, none had local recurrence alone and only two had both local and distant metastasis as the initial sites of disease progression. CONCLUSIONS: IP following concurrent EP plus twice-daily TRT is safe with acceptable toxicities. A randomized phase III trial comparing EP with IP following EP plus concurrent TRT for LSCLC is ongoing (JCOG0202).     

Cisplatin plus etoposide chemotherapy followed by thoracic irradiation and paclitaxel plus cisplatin consolidation therapy for patients with limited stage small cell lung carcinoma

PURPOSE: To evaluate the efficacy and tolerance of a cisplatin plus etoposide regimen followed by thoracic radiotherapy (TRT) and paclitaxel plus cisplatin consolidation chemotherapy in patients with limited stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-nine patients with limited SCLC were enrolled onto this study. Patients received three courses of cisplatin 75 mg/m2 i.v., day 1 and etoposide 100 mg/m2 i.v., days 1-3 (EP regimen), followed by TRT (45-56 Gy administered in 15 fractions), and three courses of paclitaxel 175 mg/m2 i.v., day 1 and cisplatin, as previously, on day 2 (PP regimen); cycles were repeated every 21 days. RESULTS: All patients were evaluable for toxicity and 34 for response. The overall response rate was 67% (CR: 26%; PR: 41%; intention-to-treat analysis) (95% CI: 53.0-84.2%). After a median follow-up period of 15 months, the median survival time was 15 months, the median time to tumor progression 8.3 months and the 1-year survival rate 53.8%. Grade 3/4 neutropenia occurred in 39% and 36% of patients receiving EP and PP regimens, respectively. The incidence of febrile neutropenia was 5% and 3% for EP and PP regimens, respectively. Other hematologic and non-hematologic toxicities were mild, with the exception of esophagitis occurring in 36% of patients during and/or immediately after radiotherapy. CONCLUSION: Consolidation therapy with PP after sequential EP and thoracic radiotherapy is feasible and well-tolerated; however, the efficacy results are comparable with those previously obtained in the same patients' population using a combination of EP and TRT.     

Phase II study of irinotecan plus cisplatin induction followed by concurrent twice-daily thoracic irradiation with etoposide plus cisplatin chemotherapy for limited-disease small-cell lung cancer.

PURPOSE: Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-na?ve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). PATIENTS AND METHODS: Between November 2001 and May 2003, 35 chemotherapy-na?ve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (i.v.) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 i.v. on days 43 and 64, and etoposide 100 mg/m2 i.v. on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. RESULTS: All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. CONCLUSION: IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.     

依立替康联合顺铂与足叶乙甙联合顺铂治疗广泛期小细胞肺癌的系统评价

背景与目的EP(足叶乙甙+顺铂)方案是否是广泛期小细胞肺癌的最佳化疗方案尚不确定,系统评价IP(依立替康+顺铂)方案与EP方案治疗广泛期小细胞肺癌的有效性和安全性。方法计算机检索EMBASE、PubMed、The Cochrane Library、CBM、CSJD、CJFD关于IP方案与EP方案治疗广泛期小细胞肺癌的随机对照试验(RCTS),有两名评价者独立评价纳入研究的质量并提取资料,并用RevMan5.0软件进行meta分析。结果共纳入4篇RCTS共计1180例患者。Meta分析结果显示:IP方案与EP方案治疗广泛期小细胞肺癌在1年生存率(RR=1.22,95%CI:0.97-1.54)、2年生存率(RR=2.26,95%CI:0.46-11.21)方面差异无统计学意义,两方案在总应答率(RR=1.13,95%CI:1.03-1.25)、3/4级中性粒细胞减少症(RR=0.48,95%CI:0.34-0.69)、3/4级血小板减少症(RR=0.23,95%CI:0.15-0.36)、3级贫血(RR=0.55,95%CI:0.40-0.77)、3/4级腹泻(RR=9.56,95%CI:4.91-18.59)...     

伊立替康联合顺铂方案治疗小细胞癌临床观察

背景与目的:依托泊苷联合顺铂(EP)方案是小细胞癌(SCC)全身化疗的经典方案,但其疗效仍不理想.伊立替康(CPT-11)作为抗肿瘤新药已有报道用于SCC的治疗.本研究旨在评价CPT-11联合顺铂(DDP)方案治疗SCC的近期疗效及毒性反应.方法:2006年1月-2007年12月采用CPT-11联合顺铂(DDP)方案治疗SCC患者31例,CPT-11 60 mg/m2 加入0.9%氯化钠溶液250 ml中静脉滴注,第1、8、15天给药;DDP 25 mg/m2 加入0.9%的氯化钠溶液500 ml中静脉滴注,第1～3天给药,28 d为1周期;化疗2个周期后评价疗效.结果:全组31例患者均可评价疗效,其中CR 4例、PR 15例、SD 5例、PD 7例,近期有效率为61.3%,主要毒性反应包括骨髓抑制、恶心呕吐及迟发性腹泻.结论:CPT-11联合DDP方案治疗SCC疗效确切,毒性反应可以耐受,值得进一步深入研究.     

Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study

BACKGROUND: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). METHODS: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. RESULTS: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment. CONCLUSION: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.     

Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan.

BACKGROUND: To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design. PATIENTS AND METHODS: A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP). RESULTS: The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated. CONCLUSION: The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.     

Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer

BACKGROUND: A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. PATIENTS AND METHODS: Twenty chemotherapy-na?ve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). RESULTS: The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). CONCLUSIONS: Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.     

替尼泊甙联合顺铂与足叶乙甙联合顺铂治疗小细胞肺癌的疗效比较

背景与目的:足叶乙甙(VP-16)联合顺铂(DDP)组成的EP方案是治疗小细胞肺癌(smallcelllungcancer,SCLC)的标准方案之一,但治愈率较低;替尼泊甙(VM-26)具有与VP-16同等的抗癌活性,且能通过血脑屏障。本研究的目的是观察比较VM-26联合DDP方案与EP方案治疗SCLC患者的疗效及对脑转移的预防作用。方法:70例初治、无脑转移的SCLC患者接受治疗,其中VM-26+DDP方案(VM-26组)34例,EP方案(VP-16组)36例,病人一般特征经χ2检验,两组具有可比性(P>0.05)。结果:VM-26组CR12例,PR14例,NC6例,PD2例,有效率76.5%,中位生存期10.4个月,1、2、5年生存率分别为35.3%、14.7%、8.8%;VP-16组CR12例,PR13例,NC8例,PD3例,有效率69.4%,中位生存期9.8个月,1、2、5年生存率分别为38.9%、13.9%、8.3%。两组有效率及生存期均无统计学差异(P>0.05)。VM-26组脑转移率为5.9%,VP-16组为19.4%,VP-16组明显高于VM-26组,有统计学差异(P=0.027)。不良反应主要为骨髓抑制,多为Ⅰ、Ⅱ度,两组比较无统计学差异(P>0.05)。过敏反应VM-26组高于VP-16组,有统计学差异(P=0.016)。结论:VM-26联合DDP治疗SCLC疗效肯定,其近期疗效和长期生存率与EP方案组相似;该方案对脑转移有一定的预防作用,耐受性较好,可作为初治SCLC的一线治疗方案。     

伊立替康联合顺铂与吉西他滨联合顺铂一线治疗晚期非小细胞肺癌的随机对照研究

目的　探讨伊立替康（ＣＰＴ １１）联合顺铂（ＤＤＰ）方案（ＩＰ方案）与吉西他滨（ＧＥＭ）联合ＤＤＰ方案（ＧＰ方案）一线治疗非小细胞肺癌（ＮＳＣＬＣ）的近期疗效和毒副反应。方法　采用前瞻性、开放性、随机对照的临床研究设计,纳入经组织学或细胞学确诊的初治晚期ＮＳＣＬＣ患者８８例,按２∶１比例随机分入ＩＰ方案组和ＧＰ方案组,ＩＰ方案组６０例,ＧＰ方案组２８例。ＩＰ方案组：ＣＰＴ-11 １００ｍｇ／ｍ２,ｄ１、ｄ８;ＤＤＰ２５ｍｇ／ｍ２,ｄ１ ～ｄ３;２１天为１周期。ＧＰ方案组：ＧＥＭ １０００ｍｇ／ｍ２,ｄ１、ｄ８;ＤＤＰ２５ｍｇ／ｍ２,ｄ１～ｄ３;２１天为１周期。２个周期评价疗效和不良反应。结果　ＩＰ方案组获ＰＲ２７例,ＳＤ１６例,ＰＤ１２例,死亡１例,有效率按意向性治疗分析（ＩＴＴ）为４５.０％,按符合方案分析（ＰＰ）为４８.２％,中位生存时间为１１.２个月,１年生存率为４６.４％;ＧＰ方案组获ＰＲ１０例,ＳＤ９例,ＰＤ７例,有效率按ＩＴＴ为３５.７１％,按ＰＰ为３８.５％,中位生存时间为１１.８个月,１年生存率为４６.２％。两组主要不良反应为血液学毒性、消化道反应、疲乏和脱发,ＩＰ方案组腹泻、疲乏、脱发的发生率高于ＧＰ方案组,血小板减少发生率低于ＧＰ方案组（Ｐ＜０.０５）。结论　ＩＰ方案和ＧＰ方案治疗晚期ＮＳＣＬＣ的疗效确切且无显著差异,毒副反应均可耐受。