Various factors, including renal function and the combination of nonsteroidal anti-inflammatory drugs, influence the pharmacokinetics of pemetrexed. In this study, we aimed to determine the risk factors for severe adverse events associated with pemetrexed administration. We retrospectively examined the medical records of 82 patients who received pemetrexed. Multiple logistic regression analysis indicated that a creatinine clearance (CCr) of less than 45 mL/min and administration of pemetrexed as early-line treatment were significant risk factors. We then retrospectively compared the adverse events associated with pemetrexed between patients with normal renal function (CCr≥45 mL/min) and those with impaired renal function (CCr<45 mL/min). With regard to hematological toxicity, the frequency of occurrence of grade 3 neutropenia was significantly higher among patients with a CCr of <45 mL/min. With regard to non-hematological toxicity, the frequency of occurrence of grade 2 or higher nausea was significantly higher among patients with a CCr of <45 mL/min. However, the efficacy of pemetrexed did not differ significantly between the 2 groups. Our findings suggest that, for patients with a decline in renal function (CCr <45 mL/min), attention must be paid to the possibility of serious adverse events such as neutropenia and nausea when considering the administration of pemetrexed.

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