Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China.
Lung Cancer. 2011 Aug;73(2):203-10. doi: 10.1016/j.lungcan.2010.12.006. Epub 2011 Jan 5.
To assess the risk/benefit profiles of EGFR TKIs monotherapy using erlotinib or gefitinib in comparison with single-agent chemotherapy using third-generation cytotoxics (gemcitabine, vinorelbine, taxanes) as the first-line treatment for chemonaÏve patients with advanced non-small cell lung cancer (ANSCLC) and poor performance status (PS).
A pooled analysis and systematic review was performed using trials identified through MEDLINE, EMBASE, Cochrane Library, and the Clinical-Trials.gov. Data were collected from randomized and non-randomized phase II or III clinical trials of EGFR TKIs monotherapy or single-agent chemotherapy using third-generation cytotoxics published before 3/1/2010, and the pooled estimates for efficacy and safety outcomes of interest were calculated.
Fifteen eligible trials (1425 patients) were selected from 323 studies that initially were identified. In 5 of the selected single-agent chemotherapy studies, the elderly were included together with poor PS patients. Outcomes from these studies still were employed for a thorough analysis. Targeting poor PS patients, we found that the pooled response rate (95% confidence interval) to EGFR TKIs for unselected population was 6% (3-8%), not substantially different from 9% (6-13%) reported by single-agent chemotherapy trials using third-generation cytotoxics. However, EGFR TKIs had better disease control rates with a pooled estimate of 40% (33-47%), significantly higher than 30% (20-41%) of the cytotoxics. Single-agent chemotherapy trials enrolling both elderly and poor PS patients had better results with the pooled response rate and the pooled disease control rate was 13% (11-16%) and 41% (36-46%) respectively. For safety information, despite both treatments were well-tolerated, the toxicity profile of EGFR TKIs was clearly more favorable than that reported by chemotherapy. The severe hematological adverse events related to EGFR TKIs treatment were rare. EGFR TKIs also tended to be more effective in improvement of symptoms or quality-of-life (QOL).
Although, both of the treatments had low response rates, EGFR TKIs tended to be more effective in control of tumor progression, reduction of therapy-related toxicities, improvement of symptoms or quality-of-life in the first-line treatments of ANSCLC patients with poor PS. Moreover, our data also suggest that the elderly patients without selection carefully according their PS should be separated from this population. Further investigations with valid comparison groups are necessary.
评估 EGFR-TKIs 单药治疗（厄洛替尼或吉非替尼）与第三代细胞毒药物（吉西他滨、长春瑞滨、紫杉烷类）单药化疗作为未经化疗的晚期非小细胞肺癌（NSCLC）且体能状态（PS）较差患者的一线治疗的风险/获益比。
通过 MEDLINE、EMBASE、Cochrane 图书馆和 Clinical-Trials.gov 检索文献，进行荟萃分析和系统综述。收集 EGFR-TKIs 单药治疗或第三代细胞毒药物单药化疗的随机和非随机 II 或 III 期临床试验数据，这些研究在 2010 年 3 月 1 日之前发表，计算感兴趣的疗效和安全性结局的汇总估计值。
从最初确定的 323 项研究中，选择了 15 项符合条件的试验（1425 例患者）。在 5 项选定的单药化疗研究中，包括了老年患者和 PS 较差的患者。这些研究的结果仍被用于全面分析。针对 PS 较差的患者，我们发现未选择人群中 EGFR-TKIs 的总体缓解率（95%置信区间）为 6%（3-8%），与第三代细胞毒药物单药化疗试验报告的 9%（6-13%）无显著差异。然而，EGFR-TKIs 的疾病控制率更高，汇总估计值为 40%（33-47%），明显高于细胞毒药物的 30%（20-41%）。纳入老年和 PS 较差患者的单药化疗试验的结果更好，其总缓解率和总疾病控制率分别为 13%（11-16%）和 41%（36-46%）。关于安全性信息，尽管两种治疗方法均耐受良好，但 EGFR-TKIs 的毒性谱明显优于化疗报告的毒性谱。与 EGFR-TKIs 治疗相关的严重血液学不良事件很少见。EGFR-TKIs 也倾向于更有效地改善症状或生活质量（QOL）。
尽管两种治疗方法的缓解率均较低，但 EGFR-TKIs 更有效地控制肿瘤进展，降低治疗相关毒性，改善 PS 较差的晚期 NSCLC 患者的症状或生活质量。此外，我们的数据还表明，未经仔细选择 PS 的老年患者应与该人群分开。需要进行进一步的研究以建立有效的对照组。
