Department of Oncology, Humanitas Cancer Center, Rozzano, Italy.
Lung Cancer. 2012 Mar;75(3):360-7. doi: 10.1016/j.lungcan.2011.08.011. Epub 2011 Sep 19.
The pemetrexed-cisplatin chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). The second-line (SL) chemotherapy is considered, but the optimal treatment has not been defined yet. The aim of this study was to evaluate the clinical outcomes of SL-therapy in a series of MPM-patients included in a retrospective multicenter database. Clinical records of MPM-patients who received SL-treatment from 1996 to 2008 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL, stratified for patient characteristics, FL-outcomes, and type of SL. Out of 423 patients, 181 with full clinical data were identified. Patients' characteristics: median-age 64 years (range: 36-85); male gender 115 (63.5%); good EORTC-score 109 (60.2%); epithelial histology 135 (74.6%). After FL, 147 (81.2%) patients achieved disease-control (DC) and 45 had a time-to-progression≥12 months (TTP≥12). After SL, 95 patients (52.6%) achieved DC (21 response; 74 stable-disease); median PFS and OS were 4.3 and 8.7 months, respectively. According to multivariate analysis, DC after SL-therapy was significantly related to pemetrexed-based treatment (OR: 2.46; p=0.017) and FL-TTP≥12 (OR: 3.50; p=0.006). PFS was related to younger age (<65 years) (HR: 0.70; p=0.045), ECOG-PS0 (HR: 0.67; p=0.022), and FL-TTP≥12 (HR: 0.45; p<0.001). OS was significantly related to ECOG-PS0 (HR: 0.43; p<0.001) and to FL-TTP≥12 (HR: 0.54; p=0.005). In pemetrexed pre-treated patients, re-treatment with a pemetrexed/platinum combination significantly reduced the risk-of-death than pemetrexed alone (HR: 0.11; p<0.001). In conclusion, SL-chemotherapy seems to be active in MPM-patients, particularly in younger patients with ECOG-PS0 and prolonged TTP after FL-pemetrexed-based chemotherapy. In selected patients, re-challenge with pemetrexed-based regimens, preferentially associated with platinum-compound, appears to be an option for SL-setting. Considering the important limitations of this study, due to retrospective nature and the possible selection bias, prospective clinical trials are warranted to clarify these issues.
培美曲塞联合顺铂化疗是恶性胸膜间皮瘤（MPM）一线（FL）治疗的标准治疗方法。二线（SL）化疗被认为是有效的，但最佳治疗方法尚未确定。本研究旨在评估纳入回顾性多中心数据库的一系列 MPM 患者的 SL 治疗的临床结果。回顾了 1996 年至 2008 年间接受 SL 治疗的 MPM 患者的临床记录。研究终点为 SL 治疗的反应、总生存期（OS）和无进展生存期（PFS），根据患者特征、FL 结果和 SL 类型进行分层。在 423 名患者中，确定了 181 名具有完整临床数据的患者。患者特征：中位年龄 64 岁（范围：36-85）；男性 115 名（63.5%）；EORTC 评分良好 109 名（60.2%）；上皮组织学 135 名（74.6%）。FL 后，147 名（81.2%）患者达到疾病控制（DC），45 名患者进展时间≥12 个月（TTP≥12）。SL 后，95 名患者（52.6%）达到 DC（21 例有反应；74 例疾病稳定）；中位 PFS 和 OS 分别为 4.3 个月和 8.7 个月。根据多变量分析，SL 治疗后的 DC 与培美曲塞为基础的治疗（OR：2.46；p=0.017）和 FL-TTP≥12（OR：3.50；p=0.006）显著相关。PFS 与年龄较小（<65 岁）（HR：0.70；p=0.045）、ECOG-PS0（HR：0.67；p=0.022）和 FL-TTP≥12（HR：0.45；p<0.001）相关。OS 与 ECOG-PS0（HR：0.43；p<0.001）和 FL-TTP≥12（HR：0.54；p=0.005）显著相关。在培美曲塞预处理的患者中，培美曲塞/铂类联合再治疗显著降低了死亡风险（HR：0.11；p<0.001）。总之，SL 化疗似乎对 MPM 患者有效，特别是在 ECOG-PS0 较低且 FL 培美曲塞为基础化疗后 TTP 延长的年轻患者中。在选定的患者中，重新使用培美曲塞为基础的方案，最好与铂类化合物联合使用，似乎是 SL 治疗的一种选择。考虑到本研究的重要局限性，由于回顾性和可能存在选择偏倚，需要进行前瞻性临床试验来阐明这些问题。
