Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study
Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study
复制标题
DOI：
10.1016/s1470-2045(13)70511-4
复制
发表时间：
2014-01-01
期刊：
影响因子：
51.1
通讯作者：
Tamura, Tomohide
中科院分区：
文献类型：
--
作者：
Kubota, Kaoru;Hida, Toyoaki;Tamura, Tomohide
背景：四个周期的依托泊苷联合顺铂和加速超分割胸部放疗（AHTRT）是局限期小细胞肺癌（SCLC）的标准治疗方案。与依托泊苷联合顺铂相比，伊立替康联合顺铂显著改善了广泛期SCLC的总生存期。我们比较了这些方案与有限阶段SCLC.Methods患者的总生存率，我们在日本的36个机构进行了3期研究。入选标准包括年龄20-70岁，东部肿瘤协作组（ECOG）体能状态评分为0-1，器官功能良好。符合条件的既往未经治疗的有限期SCLC患者接受一个周期的依托泊苷+顺铂（第1-3天静脉注射依托泊苷100 mg/m2;第1天静脉注射顺铂80 mg/m2）+AHTRT（1.5戈伊，每日两次，每周5天，共45戈伊，持续3周）。将诱导治疗后无疾病进展的患者随机分组，（一句：1比值，使用最小化方法，使用偏倚硬币分配平衡ECOG体能状态[0 vs 1]、诱导放化疗缓解[完全缓解+接近完全缓解vs部分缓解和疾病稳定]，和机构）接受另外三个周期的巩固依托泊苷+顺铂或伊立替康+顺铂（第1、8、15天静脉注射伊立替康60 mg/m2;第1天静脉注射顺铂60 mg/m2）。患者、医生和研究者都知道分配情况。主要终点是随机分组后的总生存率;主要分析是通过意向治疗进行的。该试验注册于ClinicalTrials.gov，编号NCT 00144989，UMIN临床试验注册处，编号C 00000095。在诱导依托泊苷+顺铂和AHTRT后，258例患者随机接受巩固依托泊苷+顺铂（n=129）或伊立替康+顺铂（n=129）。在依托泊苷联合顺铂组中，中位总生存期为3.2年（95% CI 2.4-4.1）。在伊立替康和顺铂组中，中位总生存期为2.8年（95% CI 2.4-3.6）;两组之间的总生存期无差异（风险比1.09 [95% CI 0.80-1.46]，单侧分层对数秩p=0.70）。最常见的3级或4级不良事件是中性粒细胞减少症（依托泊苷+顺铂组120例[95%] vs伊立替康+顺铂组101例[78%]），贫血（44例[35%] vs 50例[39%]）、血小板减少症（26例[21%] vs 6例[5%]）、发热性中性粒细胞减少症（21例[17%] vs 18例[14%]）和腹泻（2例[2%] vs 13例[10%]）。有一个治疗相关的不良事件导致死亡，在每个组（放射性肺炎的依托泊苷加顺铂组，脑梗死的伊立替康加顺铂组）。解释四个周期的依托泊苷加顺铂和AHTRT应继续作为标准的护理有限阶段SCLC。
Background Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC.Methods We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20-70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m(2) on days 1-3; intravenous cisplatin 80 mg/m(2) on day 1) plus AHTRT (1.5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1: 1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m(2) on days 1, 8, 15; intravenous cisplatin 60 mg/m(2) on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095.Findings 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3.2 years (95% CI 2.4-4.1). In the irinotecan and cisplatin group, median overall survival was 2.8 years (95% CI 2.4-3.6); overall survival did not differ between the two groups (hazard ratio 1.09 [95% CI 0.80-1.46], one-sided stratified log-rank p=0.70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group).Interpretation Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC.