WCLC 2025 - Posters & ePosters-P2.10.03 Long-Term Pemetrexed Administration Poses Risk of Renal Function Decline

Pdf Summary

This retrospective study examined the effects of long-term pemetrexed administration on renal function in patients treated between November 2009 and March 2024 at NHO Iwakuni Clinical Center. Pemetrexed, a cytotoxic drug used primarily to treat non-small cell non-squamous lung cancer and malignant pleural mesothelioma, is increasingly used long-term in combination with immune checkpoint inhibitors or targeted therapies. Given its nephrotoxic potential and renal excretion, the study focused on its impact on renal function decline, measured by estimated creatinine clearance.<br /><br />Among 461 cases reviewed, 351 patients who received at least two cycles with baseline creatinine clearance ≥45 mL/min were analyzed. Patients whose creatinine clearance dropped below 45 mL/min at treatment discontinuation (n=60) were compared with those who maintained clearance above this threshold (n=291). Patients experiencing renal decline tended to be older, have smaller body surface areas, and slightly lower baseline creatinine clearance. They also underwent significantly more pemetrexed administrations and experienced more dose reductions.<br /><br />Multivariate analysis highlighted that the number of pemetrexed injections was significantly correlated with a decline in creatinine clearance below 45 mL/min. Additional factors linked to renal function decline included initial creatinine clearance and dose reduction necessity. The study found that the longer duration of pemetrexed administration posed a higher risk of nephrotoxicity, consistent with previous reports identifying 10 or more cycles or cumulative doses exceeding 7000 mg as risk thresholds.<br /><br />Clinically, renal function deterioration was a common reason for pemetrexed discontinuation among affected patients, contrasting with disease progression in patients without renal decline. The findings emphasize the need for vigilant renal monitoring during long-term pemetrexed therapy, especially when combined with other treatments demonstrating efficacy.<br /><br />In conclusion, prolonged pemetrexed treatment increases the risk of renal impairment, necessitating careful assessment and management. Future research should focus on balancing pemetrexed's long-term benefits against renal safety in combination regimens.

Asset Subtitle

Tomoki Tamura

Meta Tag

Speaker Tomoki Tamura

Topic Metastatic Non-small Cell Lung Cancer – Cytotoxic Therapy

Keywords

pemetrexed

renal function

nephrotoxicity

creatinine clearance

non-small cell lung cancer

malignant pleural mesothelioma

long-term chemotherapy

dose reduction

immune checkpoint inhibitors

renal impairment risk