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Predicting Toxicity in Patients With Lung Cancer Treated With Pemetrexed

By: Joshua Swore
Posted: Monday, December 23, 2019

Based on a retrospective cohort study, published by J.G.J.V. Aerts, MD, of Erasmus Medical Center, Rotterdam, Netherlands, and colleagues, higher exposure to pemetrexed is associated with severe toxicity without an improvement in progression-free or overall survival in patients with non–small cell lung cancer. “Our findings suggest that fixed dosing reduces interpatient pharmacokinetic variability and thereby might prevent toxicity, while preserving effectiveness,” the authors stated in the European Journal of Cancer.

The researchers used population pharmacokinetic/dynamic modeling to determine whether total systemic exposure to pemetrexed can predict progression-free and overall survival. A total of 106 patients receiving first- or second-line pemetrexed for stage III or IV non–small cell lung cancer were enrolled in the study. Treatments were given in up to four cycles: 106 patients received it in cycle 1; 90 patients, in cycle 2; 73 patients, in cycle 3; and 56 patients, in cycle 4. In addition, the study included simulations to different dosing schedules to reduce estimated variability of pemetrexed exposure.

Analysis revealed that total exposure to pemetrexed with body size–based treatment did not predict overall survival (median = 9 months) or progression-free survival (median = 4.9 months) in 95 treatment-naive patients. Patients with severe chemotherapy-related adverse events (n = 55) had significantly higher pemetrexed exposure than those without such adverse events (n = 51, P < .001).

Simulations revealed that flat dosage of pemetrexed (900 mg) minimized the exposure variance across all body sizes, which predictably reduced toxicity (coefficient of variation = 18.5%) compared with body surface area–based dosing (coefficient of variation = 25%). Although the simulation suggests flat dosage may prove to be a better treatment than body size–based dosing, the authors recognize the need for a clinical trial to confirm their findings.

Disclosure: For full disclosures of other study authors, visit ejcancer.com.



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