Pemetrexed Exposure and Adverse Events in NSCLC
Posted: Thursday, May 10, 2018
Total systemic exposure to pemetrexed in patients with advanced non–small cell lung cancer (NSCLC) is significantly associated with more frequent occurrence of severe chemotherapy-related adverse events, according to research by Joachim Aerts, MD, PhD, of Erasmus MC Cancer Institute, Rotterdam, the Netherlands, and colleagues. The study, presented at the European Lung Cancer Conference (ELCC) 2018, in Geneva (Abstract 132PD), did not find a correlation between total exposure to pemetrexed and progression-free or overall survival.
“Although the impact of peak concentrations on efficacy remains unclear, our findings suggest that lower dosage might prevent severe toxicity with preservation of efficacy,” noted the investigators.
The prospective, multicenter study enrolled 165 patients with stage IIIB/IV NSCLC receiving first- or second-line pemetrexed plus platinum chemotherapy. Pemetrexed was dosed at 500 mg/m2 as a 10-minute intravenous infusion every 21 days. Plasma sampling was performed prior to and weekly after each pemetrexed administration (n = 106). A subgroup was also sampled at 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after the start of the pemetrexed infusion (n = 15). Plasma levels were analyzed to calculate an estimated AUC for each participant.
In 95 treatment-naive patients, the AUC from the first treatment cycle did not predict for overall or progression-free survival. Patients with ≥ grade 3 chemotherapy-related adverse events (n = 55) had significantly higher AUC values than did those without ≥ grade 3 chemotherapy-related adverse events.
