Sakamori Yuichi, Kim Young Hak, Yoshida Hironori, Nakaoku Takashi, Nagai Hiroki, Yagi Yoshitaka, Ozasa Hiroaki, Mishima Michiaki
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Kansai 606-8507, Japan.
Mol Clin Oncol. 2015 Mar;3(2):334-340. doi: 10.3892/mco.2014.452. Epub 2014 Nov 4.
Liver toxicity (LT) is a common side effect of pemetrexed (PEM); however, the effect of LT on clinical outcome has not been investigated in patients with non-small-cell lung cancer (NSCLC) treated with PEM. Between June, 2009 and June, 2012, a total of 95 chemo-naive NSCLC patients received a PEM-containing regimen in our hospital. We reviewed the medical records of those 95 patients and evaluated the incidence of LT. Furthermore, we investigated the association between LT and clinical outcome. In this analysis, LT was defined as any grade of aspartate aminotransferase or alanine aminotransferase elevation. A total of 67 patients (70.5%) developed LT, which occurred mostly during the first treatment cycle. Among these, 10 patients (10.5%) required a delay in treatment or a dose reduction from the subsequent cycle and PEM discontinuation was required in 1 patient. The response rate (RR) was 43.3 and 21.4% in patients with and in those without LT, respectively (P=0.0387). The median progression-free survival (PFS) and overall survival (OS) were 6.3 and 24.2 months in patients with LT and 2.9 and 18.3 months in patients without LT, respectively (P<0.0001 for PFS and P=0.2426 for OS). The multivariate analysis demonstrated that LT exerted a significant positive effect on PFS (hazard ratio = 0.341; P<0.0001). In conclusion, LT was frequently observed in NSCLC patients treated with PEM; however, it was generally easily manageable. The improvement in RR and PFS observed in patients with LT suggested that LT may be a useful predictor of a favorable outcome in this patient population.
肝毒性（LT）是培美曲塞（PEM）常见的副作用；然而，LT对接受PEM治疗的非小细胞肺癌（NSCLC）患者临床结局的影响尚未得到研究。2009年6月至2012年6月期间，我院共有95例初治NSCLC患者接受了含PEM的治疗方案。我们回顾了这95例患者的病历并评估了LT的发生率。此外，我们研究了LT与临床结局之间的关联。在本分析中，LT被定义为任何级别的天冬氨酸转氨酶或丙氨酸转氨酶升高。共有67例患者（70.5%）发生了LT，大多发生在第一个治疗周期。其中，10例患者（10.5%）需要延迟治疗或从后续周期开始降低剂量，1例患者需要停用PEM。LT患者和无LT患者的缓解率（RR）分别为43.3%和21.4%（P = 0.0387）。LT患者的中位无进展生存期（PFS）和总生存期（OS）分别为6.3个月和24.2个月，无LT患者分别为2.9个月和18.3个月（PFS，P<0.0001；OS，P = 0.2426）。多变量分析表明，LT对PFS有显著的正向影响（风险比 = 0.341；P<0.0001）。总之，在接受PEM治疗的NSCLC患者中经常观察到LT；然而，它通常易于处理。LT患者RR和PFS的改善表明，LT可能是该患者群体良好结局的一个有用预测指标。
