Effect of renal function on pemetrexed-induced haematotoxicity

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Pemetrexed (PEM) is a key anticancer agent for non-small cell lung cancer, malignant pleural mesothelioma, and thymoma.
• PEM demonstrates improved efficacy and safety when combined with platinum-based agents.
• Limited data exists on PEM safety in patients with an estimated glomerular filtration rate (eGFR) of ≤45 mL/min.

Purpose of the Study:

• To investigate the impact of renal function on the safety profile of Pemetrexed-containing regimens.
• To assess the incidence of adverse events, particularly thrombocytopaenia, in patients with varying degrees of renal impairment receiving PEM.

Main Methods:

• Retrospective review of 221 patients treated with PEM between 2009 and 2014.
• Patients were stratified into three groups based on pre-treatment creatinine clearance (CLcr): <45 mL/min (Group A), 45-80 mL/min (Group B), and ≥80 mL/min (Group C).
• Adverse events, including blood cell counts and liver function tests, were analyzed up to the second cycle of treatment.

Main Results:

• A significantly higher incidence of grade 2 thrombocytopaenia was observed in Group A (<45 mL/min CLcr) compared to Groups B and C (P <0.01 and P <0.05, respectively).
• Multivariate analysis identified a CLcr of <45 mL/min as an independent risk factor for grade ≥2 thrombocytopaenia.
• No significant differences were noted in other hematological or liver function parameters across the groups.

Conclusions:

• Patients with a CLcr <45 mL/min are at a higher risk of developing grade ≥2 thrombocytopaenia when treated with Pemetrexed-containing regimens.
• Renal function, specifically CLcr, is a critical factor to consider when prescribing PEM to minimize the risk of severe thrombocytopaenia.
• Further prospective studies are warranted to confirm these findings and establish specific dose adjustments for patients with impaired renal function.