A multicenter, descriptive, retrospective study from the Netherlands found high rates of toxicity with standard-dose pemetrexed in NSCLC patients with moderate renal impairment. Findings highlight the urgent need for safer treatment strategies in this vulnerable subgroup.
This study was conducted between 2015 and 2024 across nine hospitals in the Netherlands. Patients included were diagnosed with NSCLC, received at least one cycle of standard-dose pemetrexed, and had baseline creatinine clearance (CrCL) below 45 mL/min. The study collected data on patient and treatment characteristics, hematological and non-hematological toxicity, treatment discontinuation, dose reductions, and treatment-related hospitalizations.
A total of 44 patients were included, with a median CrCL of 41.1 mL/min (interquartile range: 35.0–43.9). Most patients (n=31; 70%) did not complete four cycles of pemetrexed therapy. Among them, 14 patients (45%) discontinued treatment due to drug-related toxicity. Treatment-related hospitalization was required in 28 patients (64%). Grade 3–4 neutropenia and leukopenia occurred in 17 patients (39%), while 15 patients (34%) experienced grade 3–4 gastrointestinal toxicity.
These real-world findings highlight the significant safety concerns of using standard-dose pemetrexed in NSCLC patients with moderate renal impairment. The high rates of severe toxicity, hospitalization, and early discontinuation emphasize the need to develop safer, renal-adjusted regimens for effective immunochemotherapy in this vulnerable group.
