Effect of liver toxicity on clinical outcome of patients with non-small-cell lung cancer treated with pemetrexed

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.