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一项汇集了 National Clinical Trials Network 临床试验中关于局限期小细胞肺癌老年患者与年轻患者同期放化疗的个体患者数据的汇总分析。

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited-stage small cell lung cancer in elderly patients versus younger patients.

机构信息

Duke University Medical Center, Durham, North Carolina.

Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

出版信息

Cancer. 2019 Feb 1;125(3):382-390. doi: 10.1002/cncr.31813. Epub 2018 Oct 21.

Abstract

BACKGROUND

Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited-stage small cell lung cancer (LS-SCLC). Many patients with LS-SCLC are elderly with comorbidities.

METHODS

Individual patient data were collected from 11 phase 2 or 3 trials for LS-SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression-free survival (PFS), the rate of severe adverse events, and off-treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients).

RESULTS

Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18-1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03-1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently.

CONCLUSIONS

Elderly patients with LS-SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.

摘要

背景

铂类药物联合依托泊苷加胸部放疗后行预防性颅脑照射是局限期小细胞肺癌(LS-SCLC)的标准治疗方法。许多 LS-SCLC 患者为老年且合并多种疾病。

方法

从 1990 年至 2010 年期间,国家临床试验网络开展的 11 项 LS-SCLC 的 2 期或 3 期试验中收集了个体患者数据。主要终点为总生存期(OS);次要终点为无进展生存期(PFS)、严重不良事件发生率和治疗结束后的原因。比较了年龄在 70 岁及以上的患者(老年患者)和年龄小于 70 岁的患者(年轻患者)的结局。

结果

分析了 1049 例年轻患者(81%)和 254 例老年患者(19%)的个体患者数据。多变量模型分析显示,与年轻患者相比,老年患者 OS 更差(风险比 [HR],1.38;95%置信区间 [CI],1.18-1.63;老年患者中位 OS 为 17.8 个月;年轻患者中位 OS 为 23.5 个月),PFS 更差(HR,1.19;95%CI,1.03-1.39;老年患者中位 PFS 为 10.6 个月;年轻患者中位 PFS 为 12.3 个月)。与年轻患者相比,老年患者更易发生 5 级不良事件(8%比 3%;P <.01)和 3 级或更高级别的呼吸困难(11%比 7%;P =.03),但较少发生 3 级或更高级别的食管炎/吞咽困难(14%比 19%;P =.04)和 3 级或更高级别的呕吐(11%比 17%;P =.01)。老年患者完成治疗的比例较低,因不良事件和患者拒绝治疗而终止治疗的比例较高,且治疗期间死亡的比例较高。

结论

LS-SCLC 的老年患者 PFS 和 OS 更差,且对治疗的耐受性更差。未来的试验应纳入对老年患者的评估、对不良事件的新型监测,以及更耐受的放疗和系统治疗。

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