伊立替康联合洛铂治疗复发性广泛期小细胞肺癌（SCLC）的临床研究

目的：观察伊立替康联合洛铂方案治疗复发性小细胞肺癌（ SCLC）的疗效和毒副反应。方法：选取36例SCLC患者,予伊立替康200mg/m2加入生理盐水250ml中,稀释后静滴1.5h,第1天;洛泊35mg/m2加入5％葡萄糖500ml中,稀释后静滴2h,第1天,每21d为1个周期,2个周期后评价疗效和毒副反应。结果：36例均可评价疗效,完全缓解（ CR）1例,部分缓解（ PR）13例,疾病稳定（ SD）11例,疾病进展（ PD）11例,客观缓解率（ ORR）为38.9％,疾病控制率（ DCR）为69.4％,中位无进展生存期（ PFS）为4.6个月,中位生存期（OS）为7.8个月。毒副反应主要为血液学毒性和消化道毒性,3/4级白细胞减少、血红蛋白减少和血小板减少发生率分别为41.7％（15/36）、50.0％（18/36）、72.2％（26/36）;腹泻发生率为69.4％（25/36）,其中3、4级腹泻为13.9％（5/36）。全组无毒性相关死亡。结论：伊立替康联合洛铂方案用于治疗复发性SCLC有较好的疗效,毒副反应可耐受。     

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.     

伊立替康联合奥沙利铂治疗广泛期小细胞肺癌的临床观察

目的:观察伊立替康联合奥沙利铂治疗广泛期小细胞肺癌(SCLC)的近期疗效和毒副反应。方法:62例广泛期SCLC患者随机分为2组。治疗组32例,伊立替康120mg/m2,静脉滴入,d1、d8;奥沙利铂130mg/m2,静脉滴入,d1;3周为1个周期。对照组30例,依托泊苷80mg/m2,静脉滴入,d1～d5;奥沙利铂130mg/m2,静脉滴入,d1;3周为1个周期。分别评价近期疗效、毒副反应和生存期。结果:治疗组与对照组有效率分别为68.75%(22/32)和46.67%(14/30),χ2=3.10,P=0.08。白细胞减少发生率治疗组(71.88%,23/32)少于对照组(100%,30/30),χ2=7.73,P=0.01。腹泻发生率治疗组(31.25%,10/32)高于对照组(10.00%,3/30),χ2=4.22,P=0.04。而二组1年生存率分别为62.50%和43.33%,χ2=2.28,P=0.13。结论:伊立替康联合奥沙利铂治疗广泛期SCLC相比依托泊苷联合奥沙利铂方案疗效提高,骨髓抑制反应轻,虽然腹泻发生率高,但能够耐受。     

伊立替康或依托泊苷联合铂类药物一线治疗广泛期小细胞肺癌的meta分析

目的 评价伊立替康联合铂类（IP）方案对比依托泊苷联合铂类（EP）方案治疗广泛期小细胞肺癌（ED-SCLC）的疗效及安全性。方法 计算机检索Cochrane Library、Pubmed、Medline、CBM、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）及万方数据库,纳入IP方案与EP方案治疗ED-SCLC的随机对照试验,检索时间截止于2014年5月,由2名评价者按照纳入和排除标准独立选择文献、提取资料并评价质量。采用RevMan 5.2软件进行Meta分析。结果 最终纳入9项研究,共2229例ED-SCLC患者。与EP方案比较,IP方案治疗的1年生存率较高（OR=1.32,95%CI： 1.10~1.58,P=0.003）;两种方案客观有效率的差异无统计学意义（OR=1.13,95%CI：0.90~1.41,P=0.29）;在安全性方面,IP方案主要为消化道毒性;EP方案主要为血液学毒性。结论 与EP方案相比,IP方案可能适合于不能耐受血液毒性的ED-SCLC患者。     

伊立替康联合奈达铂一线治疗广泛期小细胞肺癌的临床观察

目的评价伊立替康(CTP-11)联合奈达铂一线治疗广泛期小细胞肺癌的疗效及不良反应。方法 48例经病理或细胞学诊断为广泛期小细胞肺癌患者接受伊立替康90mg/m2,d1、8;奈达铂80mg/m2,分3天静脉滴注。每3周为1个周期,用药至疾病进展或化疗相关毒副反应不能耐受时观察疗效。结果 48例入选患者均可评价疗效,有效率为89.6%,疾病控制率达95.8%,中位总生存期为13.5个月,中位无疾病进展时间(TTP)为7.6个月。主要不良反应为Ⅲ/Ⅳ度中性粒细胞下降(33.3%)、腹泻(16.7%)和恶心、呕吐(4.2%)等。结论伊利替康联合奈达铂一线治疗广泛期小细胞肺癌安全、有效,可作为一线化疗方案的选择。     

伊立替康联合奈达铂一线治疗广泛期小细胞肺癌的临床观察

目的评价伊立替康（CTP-11）联合奈达铂一线治疗广泛期小细胞肺癌的疗效及不良反应。方法 48例经病理或细胞学诊断为广泛期小细胞肺癌患者接受伊立替康90mg/m2,d1、8;奈达铂80mg/m2,分3天静脉滴注。每3周为1个周期,用药至疾病进展或化疗相关毒副反应不能耐受时观察疗效。结果 48例入选患者均可评价疗效,有效率为89.6%,疾病控制率达95.8%,中位总生存期为13.5个月,中位无疾病进展时间（TTP）为7.6个月。主要不良反应为Ⅲ/Ⅳ度中性粒细胞下降（33.3%）、腹泻（16.7%）和恶心、呕吐（4.2%）等。结论伊利替康联合奈达铂一线治疗广泛期小细胞肺癌安全、有效,可作为一线化疗方案的选择。     

铂类联合伊立替康与铂类联合依托泊苷一线治疗广泛期小细胞肺癌的系统评价研究

摘 要：［目的］ 采用Meta分析评价铂类联合伊立替康与铂类联合依托泊苷一线治疗广泛期小细胞肺癌的疗效,为临床用药提供参考。［方法］ 计算机检索PubMed、ClinicalTrials.gov、CNKI中文数据库,按照纳入与排除标准筛选关于铂类联合伊立替康（IP方案）与铂类联合依托泊苷（EP方案）一线治疗广泛期小细胞肺癌的临床研究,并使用RevMan5.4.1和Stata11.0进行统计分析。［结果］ IP方案一线治疗广泛期小细胞肺癌患者可显著延长总生存期,生存获益优于EP方案,合并HR为0.85（95%CI：0.78~0.92）。在亚洲人群中,相比EP方案,IP方案一线治疗可提高患者客观反应率,合并OR为1.66（95%CI：1.04~2.65）。患者对IP方案的耐受良好,治疗相关死亡的发生与EP方案无差异,OR为1.11（95%CI：0.49~2.50）。［结论］ 铂类联合伊立替康可作为小细胞肺癌的标准一线治疗方案。     

伊立替康联合顺铂治疗复发转移性卵巢癌

目的:观察伊立替康联合顺铂治疗复发转移性卵巢癌的疗效与安全性。方法:对11例复发性卵巢癌应用伊立替康200mg/m2,静滴,第1天;顺铂25 mg/m2,静滴,第1-3天,21天为1个周期,2个周期后进行一次疗效评价。结果:11例患者中完全缓解1例,部分缓解6例,总有效率为63.6%;主要不良反应为血液毒性,Ⅲ-Ⅳ度中性粒细胞下降36.3%(4/11),其次为恶心、呕吐,Ⅲ-Ⅳ度恶心、呕吐为27.3%(3/11),仅1例出现Ⅲ度腹泻。结论:伊立替康联合顺铂治疗复发转移性卵巢癌是可行、安全、有效的。     

伊立替康联合顺铂治疗复发转移性卵巢癌

目的：观察伊立替康联合顺铂治疗复发转移性卵巢癌的疗效与安全性。方法：对11例复发性卵巢癌应用伊立替康200mg／m^2,静滴,第1天;顺铂25mg／m^2,静滴,第1—3天,21天为1个周期,2个周期后进行一次疗效评价。结果：11例患者中完全缓解1例,部分缓解6例,总有效率为63．6％;主要不良反应为血液毒性,Ⅲ-Ⅳ度中性粒细胞下降36．3％（4／11）,其次为恶心、呕吐,Ⅲ-Ⅳ度恶心、呕吐为27．3％（3／11）,仅1例出现Ⅲ度腹泻。结论：伊立替康联合顺铂治疗复发转移性卵巢癌是可行、安全、有效的。     

SCLC extensive disease – treatment guidance by extent or/and biology of response?

Surgery and radiotherapy are currently accepted alternatives for the treatment of localized prostate cancer. In the absence of relevant randomized trials no decision regarding the superiority of any of the given approaches can be made. Up to now several cohort-based approaches indicate similar outcomes for both treatments. Based on a new population based approach, Merglen and co-workers recently concluded that surgery would offer the best chance of long-term control in terms of 10-year survival for T1–T3 prostate cancer patients. Unfortunately the strength of this trial is limited by several shortcomings. Most importantly, issues of radiation dosage have not been taken into account. In addition, several relevant parameters including Gleason score and PSA are not well balanced between the arms and the assignment to arbitrary risk groups does not reflect the real biological behaviour. Thus, the data provided do not support the strong conclusion issued by the authors. Based on the data available, surgery and radiotherapy still have to be considered as equally effective.     

Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study

Background

The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment.

Patients and methods

Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m² (day 1) and irinotecan 60 mg/m² (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease.

Results

Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild.

Conclusion

Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival.     

Determining carboplatin/etoposide dosage in extensive stage small-cell lung cancer (SCLC).

In order to define the maximum tolerance level of combined carboplatin/etoposide dosage, patients with extensive stage small-cell lung cancer (SCLC) were treated with a fixed dose of carboplatin (300 mg/m2 iv on day 1) and escalating doses of etoposide starting with 80 mg/m2 iv on days 1-3. Five patients were given this starting and every following dose level. The daily dose of etoposide was increased in increments of 20 mg/m2 iv until severe myelosuppression occurred in 3 of 5 patients. Leuko- or thrombocytopenia WHO grade 3 or 4 occurred in 0/5 of the patients at the dose levels of 80 and 100 mg/m2, in 1/4 of the patients at the level of 120 mg/m2, in 2/5 of the patients at a level of 140 mg/m2, and 3/5 patients at a level of 160 mg/m2. Thus, increase in dosage was stopped at an etoposide dose of 160 mg/m2. Other side effects were mild and consisted predominantly of nausea and vomiting in 14/25 of the patients. The overall response rate was 40% with a 12% complete remission rate, median survival was 9.3 months and median progression-free survival totalled 4.3 months. These results indicate that combined carboplatin/etoposide is a well tolerated regimen in extensive-stage SCLC, with response rates comparable to those of other standard protocols. Using treatment intervals of 4 weeks the recommended dose of etoposide in combination with 300 mg/m2 carboplatin was identified as 140 mg/m2 iv for 3 consecutive days.     

Phase II study of dose-intense chemotherapy with sequential topoisomerase-targeting regimens with irinotecan/oxaliplatin followed by etoposide/carboplatin in chemotherapy naive patients with extensive small cell lung cancer

Introduction

Topoisomerase inhibitors are active agents in small cell lung cancer (SCLC), and preclinical models indicate that sequential administration of a topoisomerase I inhibitor followed by a topoisomerase II inhibitor can result in enhanced cytotoxicity.

Patients and methods

In this phase II study, patients with extensive SCLC were treated with two sequential topoisomerase-based regimens: irinotecan (150 mg/m²)/oxaliplatin (85 mg/m²) [regimen A] on day 1 followed by etoposide (100 mg/m² × 3)/carboplatin (AUC 6) [regimen B] on day 15. Regimen A was repeated 3 weeks later. The primary objective was objective response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and exploratory correlative analysis of the tumor expression of the excision repair cross complementing (ERCC1) and topoisomerase II-α. Patients received a maximum of 5 cycles of sequential therapy of regimen A → B.

Results

The overall response rate was 96%, the 6-month PFS was 76.9%, the median PFS was 8.95 months, and OS was 12.9 months in 26 evaluable patients. Grade 4 neutropenia (23%) and thrombocytopenia (58%) were observed with regimen B; and grade 2/3 nausea-vomiting (54%) and diarrhea (46%) with regimen A. Seven patients required dose reductions in regimen A and 19 patients in regimen B. The dose intensity, delivered during the first three cycles was 89%. No significant correlations were observed between the tumor expression of the ERCC1 and topoisomerase II-α and clinical outcomes (PFS or OS).

Conclusions

Although cross-study comparisons are difficult to make, our data suggests that sequential topoisomerase-targeting regimens may enhance the efficacy of chemotherapy in newly diagnosed SCLC patients (Clinical Trial Registration Number, 9 NCT00240097; Clinical Trials.gov number, NCT00240097).     

广泛期小细胞肺癌一线化疗肿瘤缓解深度与生存期的相关性

目的:分析广泛期小细胞肺癌一线化疗后肿瘤缓解深度与患者生存期的相关性。方法:回顾性分析符合入组条件的50例初治广泛期小细胞肺癌患者的临床资料。通过Spearman秩相关检验评价广泛期小细胞肺癌化疗后肿瘤缓解深度与生存期的相关性，应用Log-rank检验比较不同肿瘤缓解深度对生存期的影响，应用COX比例回归模型进行多因素分析。结果:Spearman秩相关分析显示肿瘤缓解深度与PFS及OS均呈中等程度相关。不同缓解深度患者的生存期存在统计学差异。体重减少（P＜0.000 1）、缓解深度（P＜0.001）为无进展生存期的独立影响因素；体重减少（P＜0.000 1）、体力状态（P=0.001 2）、缓解深度（P＜0.001）、化疗周期（P=0.000 2）、二线治疗（P=0.006 7）为总生存期的独立预后因素。结论:广泛期小细胞肺癌一线化疗后肿瘤缓解深度对患者生存期有一定的预测价值。