Shen Lan, Niu Xiaomin, Jian Hong, Xu Yunhua, Yu Yongfeng, Lu Shun
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Xuhui District, Shanghai, 200030, PR China.
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Xuhui District, Shanghai, 200030, PR China.
Lung Cancer. 2017 Sep;111:43-50. doi: 10.1016/j.lungcan.2017.07.001. Epub 2017 Jul 4.
Pemetrexed continuation maintenance therapy after induction with platinum-based chemotherapy is a standard treatment option for non-squamous non-small cell lung cancer (NSCLC) patients. However, discontinuation of maintenance therapy is still a challenge in clinical practice. We aimed to investigate interfering factors and clinical risk associated with discontinuation of pemetrexed maintenance therapy (PMT).
Data of patients with locally advanced or metastatic non-squamous NSCLC who received PMT between December 2011 and October 2015 were retrospectively analyzed. Patients' characteristics, performance status (PS), response and toxicity evaluation were collected. The reasons for PMT discontinuation were summarized. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and Cox proportional hazard model.
Of the 220 patients included for final analysis, 132 patients (60.0%) continued PMT until disease progression. The patients over 60 years old (p=0.021), the patients with PS 2 at the initiation of PMT (p=0.005) and the patients experienced grade 3/4 toxicity during PMT (p<0.001) had a higher discontinuation rate. The reasons for PMT discontinuation were the regarding toxicity (39.8%), high intensity of hospital visit (17.0%), treatment cost (13.6%), patients' preference (26.1%) and failure of pain control (3.4%). In univariate analysis, PS 0-1 at the initiation of PMT (5.6 versus 4.3 months, p=0.022) and PMT continuation (5.6 versus 4.3 months, p<0.001) were associated with improved PFS. And PMT continuation was associated with improved OS (19.2 versus 16.8 months, p=0.003) along with actionable mutations and PS 0-1 at the initiation of PMT. In multivariate analysis, PMT continuation (hazard ratio: 1.486; 95% CI: 1.050-2.104; p=0.025) was an independent prognostic factor regarding OS benefit assessed by Cox proportional hazard model.
Discontinuation of PMT is common in clinical practice. The survival benefit suggests that fit patients should be encouraged to continue PMT until disease progression.
对于非鳞状非小细胞肺癌（NSCLC）患者，以铂类为基础的化疗诱导后培美曲塞持续维持治疗是一种标准的治疗选择。然而，在临床实践中，维持治疗的中断仍然是一个挑战。我们旨在调查与培美曲塞维持治疗（PMT）中断相关的干扰因素和临床风险。
回顾性分析2011年12月至2015年10月期间接受PMT的局部晚期或转移性非鳞状NSCLC患者的数据。收集患者的特征、体能状态（PS）、反应和毒性评估。总结PMT中断的原因。采用Kaplan-Meier法和Cox比例风险模型分析无进展生存期（PFS）和总生存期（OS）。
纳入最终分析的220例患者中，132例（60.0%）持续接受PMT直至疾病进展。60岁以上的患者（p = 0.021）、PMT开始时PS为2的患者（p = 0.005）以及在PMT期间经历3/4级毒性的患者（p < 0.001）中断率较高。PMT中断的原因包括毒性（39.8%）、就诊强度高（17.0%）、治疗费用（13.6%）、患者偏好（26.1%）和疼痛控制不佳（3.4%）。单因素分析中，PMT开始时PS为0 - 1（5.6个月对4.3个月，p = 0.022）和持续接受PMT（5.6个月对4.3个月，p < 0.001）与PFS改善相关。并且PMT持续与OS改善相关（19.2个月对16.8个月，p = 0.003），同时伴有可操作的突变和PMT开始时PS为0 - 1。多因素分析中，通过Cox比例风险模型评估，PMT持续（风险比：1.486；95%可信区间：1.050 - 2.104；p = 0.025）是OS获益的独立预后因素。
在临床实践中，PMT中断很常见。生存获益表明，适合的患者应被鼓励持续接受PMT直至疾病进展。
