Severity and predictive factors of adverse events in pemetrexed-containing chemotherapy for non-small cell lung cancer

Pemetrexed is a key anticancer agent for treatment of advanced non-small cell lung cancer (NSCLC). Pemetrexed is generally well tolerated, but individual-patient differences exist in severity of adverse events. Our study aimed to characterize the adverse events of pemetrexed that result in discontinuation of chemotherapy and to identify risk factors associated with those adverse events. We retrospectively studied the incidence of adverse events in 257 patients with NSCLC who received pemetrexed (P) with or without bevacizumab (B) and/or carboplatin (C): P, PB, CP, or CPB. Patients whose chemotherapy was discontinued were divided into two groups according to adverse events and disease progression. Grade 2/3 nausea, fatigue with P and PB, and rash with CP and CPB occurred more frequent in the adverse events group than in the disease progression group. Multivariate analysis indicated that grade 2/3 nausea [odds ratio (OR) 9.94; 95% confidence interval (CI) 1.46–67.37; p = 0.01] and fatigue (OR 10.62; CI 1.60–70.20; p = 0.01) with P or PB, and rash (OR 6.12; CI 1.34–27.88; p = 0.01) with CP or CPB, were independent risk factors for discontinuation of chemotherapy. Administration of dexamethasone at doses less than 4 mg after the day of pemetrexed administration was associated with nausea following P or PB (OR 11.08; 95% CI 1.02–119.95; p = 0.04). Grade 2/3 nausea and fatigue with P or PB, and rash with CP or CPB, were associated with discontinuation of chemotherapy.