The MILES-2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non-small cell lung cancer elderly patients
The MILES-2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non-small cell lung cancer elderly patients
复制标题
DOI：
10.1016/j.lungcan.2007.12.002
复制
发表时间：
2008-07-01
期刊：
影响因子：
5.3
通讯作者：
Perrone, Francesco
中科院分区：
文献类型：
--
作者：
Gridelli, Cesare;De Maio, Ermelinda;Perrone, Francesco
背景：吉西他滨在老年晚期非小细胞肺癌（NSCLC）患者中的应用已被广泛研究。长期持续输注（10mg/m(2)/min）可提高其疗效。本研究的目的是描述单药吉西他滨长期输注治疗老年晚期NSCLC患者的活性和毒性。患者和方法：年龄≥70岁，IV期或IIIB期（积液/锁骨上淋巴结）非小细胞肺癌，预后良好（ECOG分级0或1），从未接受过化疗的患者。吉西他滨在每个周期的第1天和第8天以1200mg/m(2)的剂量延长输注（10mg/m(2)/min）。疗程每21天重复一次，最多6个周期，除非疾病进展或严重毒性。采用单阶段2期设计，51例患者需要估计25%+/- 10%的缓解率。需要10个反应来定义治疗是积极的。结果：51例患者入组，中位年龄76岁（范围70-83岁）。观察到2例完全缓解和7例部分缓解，总缓解率为17.6%（95%精确ci: 8.4-30.9%）。疾病进展的中位时间为16.1周（95% ci: 11.1-20.6），中位总生存期为41.3周（95% ci: 27.6-50.6）。由于出血和肝毒性，有2例中毒性死亡，1例缺血性中风。其他非血液学毒性是：疲劳（44%的患者），2-3级肺毒性（8%），2-3级肝毒性（16%）。恶心、口炎轻微，无心脏毒性。血液学毒性轻微，无发热性中性粒细胞减少病例。结论：长时间持续输注吉西他滨产生了比研究设计要求的应答率塔，不应再对老年晚期NSCLC患者的治疗感兴趣。2007爱思唯尔爱尔兰有限公司版权所有。
Background: Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10mg/m(2)/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC.Patients and methods: Patients aged 70 years or older, with stage IV or IIIB (effusion/supraclavicular nodes) NSCLC, good performance status (0 or 1 according to ECOG classification) who had never received chemotherapy were eligible. Gemcitabine was administered at the dose of 1200mg/m(2) by prolonged infusion (10mg/m(2)/min) on days 1 and 8 of each cycle. Courses were repeated every 21 days, for a maximum of 6 cycles, unless disease progression or severe toxicity. A single stage phase 2 design was applied, with 51 patients required to estimate a 25%+/- 10% response rate. Ten responses were required to define the treatment as active.Results: Fifty-one patients were enrolled, with a median age of 76 years (range 70-83). Two complete responses and seven partial responses were observed, for an overall response rate of 17.6% (95% exact C.I.: 8.4-30.9%). The median time to disease progression was 16.1 weeks (95% C.I.: 11.1-20.6) and the median overall survival was 41.3 weeks (95% C.I.: 27.6-50.6). There were 2 toxic deaths, due to bleeding and liver toxicity, and one patient had an ischemic stroke. Other non-haematological toxicities were: fatigue (44% of patients), grade 2-3 pulmonary toxicity (8%), grade 2-3 hepatic toxicity (16%). Nausea and stomatitis were mild and no cases of cardiac toxicity were observed. Haematological toxicity was mild, with no case of febrile neutropenia.Conclusion: Gemcitabine at prolonged constant infusion produced a response rate tower than that required by study design and should no longer be of interest for the treatment of elderly patients with advanced NSCLC. (c) 2007 Elsevier Ireland Ltd. All rights reserved.