Department of Internal Medicine, Chonnam National University Hwasun Hospital, South Korea.
Department of Pathology, Chonnam National University Hospital, Gwangju, South Korea.
Thorac Cancer. 2019 Apr;10(4):942-949. doi: 10.1111/1759-7714.13033. Epub 2019 Mar 12.
We determined the clinical characteristics and predictive factors of long-term response to pemetrexed maintenance therapy as first-line treatment for non-small cell lung cancer (NSCLC).
A total of 950 advanced NSCLC patients received pemetrexed (500 mg/m ) plus cisplatin (60 mg/m ) (Pem-Cis) induction chemotherapy every three weeks as first-line treatment between January 2010 and August 2018. Patients who did not show progression after four cycles of Pem-Cis and received at least one cycle of pemetrexed maintenance were recruited (n = 199).
Patients were divided into subgroups according to total cycles of pemetrexed: ≤ 10 (F10, n = 134) and > 10 (M10, n = 65). The M10 group had a higher proportion of patients with stage M1a (intrathoracic metastasis alone) and exhibited lower levels of thymidylate synthase (TS) than the F10 group (median H-score 10.0% vs. 60.0%; P = 0.031). Further subgrouping identified extreme responders: ≤ 7 (F7, n = 101) and ≥ 20 (M20, n = 26) cycles. The M20 group showed lower mean serum CEA levels before (17.5 vs. 147.0; P = 0.099) and after (6.9 vs. 53.2; P = 0.001) Pem-Cis treatment, and a higher incidence of normalization after Pem-Cis (abnormal 41.7% vs. 68.5%; P = 0.015). M1a stage, normalization of CEA levels after Pem-Cis, and lower TS H-score were predictors of progression-free survival in patients administered pemetrexed maintenance.
M1a stage and lower TS expression were predictors of long-term response to pemetrexed maintenance. CEA normalization after Pem-Cis could be an additional surrogate marker of positive response to long-term treatment.
我们确定了培美曲塞维持治疗作为非小细胞肺癌（NSCLC）一线治疗的长期反应的临床特征和预测因素。
2010 年 1 月至 2018 年 8 月期间，共有 950 名晚期 NSCLC 患者接受培美曲塞（500 mg/m ）加顺铂（60 mg/m ）（培美曲塞+顺铂）每 3 周诱导化疗作为一线治疗。在完成 4 个周期的培美曲塞+顺铂且至少接受 1 个周期的培美曲塞维持治疗后未出现进展的患者中招募了患者（n = 199）。
根据培美曲塞的总周期将患者分为亚组：≤ 10 个周期（F10，n = 134）和 > 10 个周期（M10，n = 65）。M10 组患者中单纯胸腔内转移的 M1a 期患者比例较高，且胸苷酸合成酶（TS）水平低于 F10 组（中位数 H 评分 10.0% vs. 60.0%；P = 0.031）。进一步亚组分析发现极反应者：≤ 7 个周期（F7，n = 101）和 ≥ 20 个周期（M20，n = 26）。M20 组患者培美曲塞+顺铂治疗前后平均血清 CEA 水平较低（治疗前 17.5 vs. 147.0；P = 0.099）和（治疗后 6.9 vs. 53.2；P = 0.001），培美曲塞+顺铂治疗后 CEA 正常化发生率较高（异常 41.7% vs. 68.5%；P = 0.015）。M1a 期、培美曲塞+顺铂后 CEA 水平正常化和较低的 TS H 评分是接受培美曲塞维持治疗的患者无进展生存期的预测因素。
M1a 期和较低的 TS 表达是培美曲塞维持治疗长期反应的预测因素。培美曲塞+顺铂治疗后 CEA 正常化可能是长期治疗反应阳性的另一个替代标志物。
