Shima Yusuke, Yoshida Hironori, Suminaga Keiichiro, Yoshida Hiroshi, Hashimoto Kentaro, Ogimoto Tatsuya, Hosoya Kazutaka, Ajimizu Hitomi, Funazo Tomoko, Nomizo Takashi, Ozasa Hiroaki, Hirai Toyohiro
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
BMC Cancer. 2025 Mar 4;25(1):388. doi: 10.1186/s12885-025-13785-x.
Pemetrexed is a key treatment for non-small-cell lung cancer (NSCLC), and its usage is increasing. However, owing to treatment-related fatality in a patient with severe renal impairment observed during an initial clinical trial, such patients were excluded from further studies. Consequently, data on the safety and efficacy of pemetrexed in these patients are limited. This study aimed to assess the use of pemetrexed in this patient group in a clinical setting.
We conducted a retrospective analysis of patients with lung cancer treated with pemetrexed at Kyoto University Hospital from April 2008 to April 2023. The patients were categorized into two groups: those who received pemetrexed with platinum derivatives (n = 349) and those who received pemetrexed alone (n = 142). Both groups were further divided into creatinine clearance (CCr) > 45 and ≤ 45 mL/min subgroups, and safety and efficacy were compared between the subgroups. The correlation between renal impairment and adverse events was evaluated through chi-square test. Univariate and logistic regression analyses were used to identify the independent risk factors for severe adverse events (SAEs) related to renal impairment. We also analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test.
A significant increase in the incidence of grade 3 or higher anemia was observed in the CCr ≤ 45 mL/min subgroups of both the platinum-concomitant and pemetrexed-alone groups (p = 0.03 and p < 0.01, respectively). No significant differences were observed in other SAEs. Multivariate analysis showed that baseline hemoglobin levels were an independent predictor of grade 3 or higher anemia across both treatment groups, alongside a baseline CCr ≤ 45 mL/min in the pemetrexed-alone group. No significant differences were observed in the overall response rate, PFS, or OS between the CCr > 45 and CCr ≤ 45 mL/min subgroups in either treatment group.
Although severe anemia was more common in patients with renal impairment, the efficacy of treatment did not differ, indicating that pemetrexed remains a viable treatment option for this population with proper management.
培美曲塞是治疗非小细胞肺癌（NSCLC）的关键药物，其使用量正在增加。然而，由于在一项初始临床试验中观察到一名严重肾功能不全患者出现与治疗相关的死亡，此类患者被排除在进一步研究之外。因此，培美曲塞在这些患者中的安全性和有效性数据有限。本研究旨在评估培美曲塞在临床环境中对此类患者群体的使用情况。
我们对2008年4月至2023年4月在京都大学医院接受培美曲塞治疗的肺癌患者进行了回顾性分析。患者分为两组：接受培美曲塞联合铂类衍生物治疗的患者（n = 349）和单独接受培美曲塞治疗的患者（n = 142）。两组患者又进一步分为肌酐清除率（CCr）> 45和≤ 45 mL/min亚组，并比较各亚组之间的安全性和有效性。通过卡方检验评估肾功能损害与不良事件之间的相关性。采用单因素和逻辑回归分析确定与肾功能损害相关的严重不良事件（SAEs）的独立危险因素。我们还使用对数秩检验分析无进展生存期（PFS）和总生存期（OS）。
在铂类联合治疗组和单独使用培美曲塞治疗组的CCr≤ 45 mL/min亚组中，3级或更高等级贫血的发生率均显著增加（分别为p = 0.03和p < 0.01）。在其他SAEs方面未观察到显著差异。多因素分析表明，基线血红蛋白水平是两个治疗组中3级或更高等级贫血的独立预测因素，在单独使用培美曲塞治疗组中，基线CCr≤ 45 mL/min也是独立预测因素。在任何一个治疗组中，CCr > 45和CCr≤ 45 mL/min亚组之间的总缓解率、PFS或OS均未观察到显著差异。
尽管严重贫血在肾功能不全患者中更为常见，但治疗效果并无差异，这表明在适当管理下，培美曲塞仍然是该人群可行的治疗选择。
