首页 > 文章详情

《柳叶刀肿瘤分册》：化疗敏感的复发性小细胞肺癌顺铂、依托泊苷、伊立替康联合化疗效果如何？

2016年06月15日

编译：南南和北北

来源：桓兴医讯

背景（Background）

依托泊苷和伊立替康是治疗小细胞肺癌的关键药物。我们在化疗敏感的复发性小细胞肺癌患者中进行了这项研究，旨在了解作为二线化疗，顺铂、依托泊苷、伊立替康联合化疗是否优于托泊替康单药化疗。

Etoposide and irinotecan are key drugs in the treatment of small-cell lung cancer. We did this study to investigate whether combined chemotherapy with cisplatin, etoposide, and irinotecan was superior to topotecan monotherapy as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer.

方法（Methods）

我们在日本的29家医疗机构进行了这项开放标签、多中心、随机3期试验。符合条件参试的小细胞肺癌患者为，对一线治疗有反应，但完成一线治疗后至少90天就表现出疾病复发或进展，入组患者随机分组（1：1）到顺铂、依托泊苷、伊立替康联合化疗组或托泊替康单药化疗组。通过最小化法进行随机分组，并对ECOG体能状态评分、入组时分期和受试者机构来源用偏币法进行随机化均衡（并不是分层或分亚组哦,看到国内众多的译文将类似的句子理解为分层或分亚组。——译者注）。联合化疗由5个疗程组成，每个疗程2周，为静脉用顺铂25mg/m2，第1、8天，静脉用依托泊苷60mg/m2，第1-3天，静脉用伊立替康90mg/m2，第8天，并自第1个疗程第9天开始，皮下注射粒细胞集落刺激因子（给化疗药物的当天除外）。托泊替康化疗由4个疗程组成，3周一疗程，每疗程于第1-5天静脉用托泊替康1.0mg/m2。主要终点为意向治疗患者群中的总生存期，采用单尾分析，α设为5%，在所有接受过至少1次剂量研究药物的所有患者中评价安全性。本试验通过“大学医院医学信息网络临床试验注册处（UMIN-CTR）”注册，注册号UMIN000000828。

We did this open-label, multicentre, randomised phase 3 trial at 29 institutions in Japan. Patients with small-cell lung cancer that responded to first-line treatment but showed evidence of disease relapse or progression at least 90 days after completion of the first-line treatment were eligible to participate. Enrolled patients were randomly assigned (1:1) to receive combination chemotherapy with cisplatin plus etoposide plus irinotecan or topotecan alone. Randomisation was done via the minimisation method with biased-coin balancing for Eastern Cooperative Oncology Group performance status, disease stage at enrolment, and institution. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m2 on days 1 and 8, intravenous etoposide 60 mg/m2 on days 1–3, and intravenous irinotecan 90 mg/m2 on day 8, with granulocyte colony-stimulating factor given by hypodermic injection every day starting from day 9 of the first course (except on the days anticancer drugs were given). Topotecan therapy consisted of four courses of intravenous topotecan 1·0 mg/m2 on days 1–5, every 3 weeks. The primary endpoint was overall survival in the intention-to-treat population, which was analysed with a one-sided α of 5%, and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number UMIN000000828.

结果（Findings）

2007年9月20日至2012年11月30日，入组了180名患者，每个治疗组各90名。患者的中位随访期22.7个月（IQR 20.0–35.3）。联合化疗组总生存期（中位值18.2个月，95%CI15.7-20.6）明显长于托泊替康组（12.5个月，10.8–14.9，风险比0.67，90%CI0.51–0.88，p=0.0079）。最常见的3、4级不良反应为中性粒细胞减少症（联合化疗组75名[83%]对比托泊替康组77名[86%]）、贫血（76名[84%]vs25名[28%]）和白细胞减少症（72名[80%]vs46名[51%]）。联合化疗组比托泊替康组3、4级粒细胞减少性发热更常见（28名[31%]vs6名[7%]），3、4级血小板减少症也如此（37名[41%]vs25名[28%]）。托泊替康组报告4名（4%）患者有严重不良反应，联合化疗组9名（10%）。托泊替康组发生2例治疗相关性死亡（局限性肺炎和肺部感染各1例），联合化疗组发生1例（粒细胞减少性发热伴脓毒症）。

Between Sept 20, 2007, and Nov 30, 2012, 180 patients were enrolled, with 90 assigned to each treatment group. The median follow-up for censored patients was 22·7 months (IQR 20·0–35·3). Overall survival was significantly longer in the combination chemotherapy group (median 18·2 months, 95% CI 15·7–20·6) than in the topotecan group (12·5 months, 10·8–14·9; hazard ratio 0·67, 90% CI 0·51–0·88; p=0·0079). The most common grade 3 or 4 adverse events were neutropenia (75 [83%] patients in the combination chemotherapy group vs 77 [86%] patients in the topotecan group), anaemia (76 [84%] vs 25 [28%]), and leucopenia (72 [80%] vs 46 [51%]). Grade 3 or 4 febrile neutropenia was more common in the combination chemotherapy group than in the topotecan group (28 [31%] vs six [7%]), as was grade 3 or 4 thrombocytopenia (37 [41%] vs 25 [28%]). Serious adverse events were reported in four (4%) patients in the topotecan group and nine (10%) in the combination chemotherapy group. Two treatment-related deaths (one each of pneumonitis and pulmonary infection) occurred in the topotecan group and one (febrile neutropenia with sepsis) occurred in the combination chemotherapy group.

解释（Interpretation）

可以考虑将顺铂、依托泊苷、伊立替康联合化疗作为化疗敏感的复发性小细胞肺癌患者的标准二线化疗方案。

Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered the standard second-line chemotherapy for selected patients with sensitive relapsed small-cell lung cancer.

责任编辑：Dr.q

2016年06月20日

郭大夫

厦门市妇幼保健院 | 医学影像科

主要化疗药物的副作用

2016年06月20日

郭大夫

厦门市妇幼保健院 | 医学影像科

学习了

2016年06月20日

郭大夫

厦门市妇幼保健院 | 医学影像科

小细胞化疗应该还算比较敏感吧