New research in the Netherlands suggests that patients who would not normally be prescribed Alimta for mesothelioma could still benefit from the gold standard mesothelioma treatment. The key is an alternate dosing strategy.
Alimta is a powerful drug that works by blocking a molecule needed for cell replication. Right now, doctors do not recommend Alimta for mesothelioma in people with poor kidney function.
But Dutch pharmacology experts now say it is possible to adjust the dosing to make Alimta safer for these mesothelioma patients.
Alimta for Mesothelioma: Proper Dosing is Key
The FDA approved Alimta for mesothelioma in 2004. Alimta (pemetrexed) is still the only drug approved for the treatment of malignant mesothelioma. It has also been approved to treat non-small cell lung cancer.
Alimta works by disrupting the production of folate, which is needed for cell replication. Alimta affects both cancer cells and normal cells, so proper dosing is critical. Even though Alimta is the gold standard for mesothelioma treatment, it is not safe for every patient.
The job of the kidneys is to filter the blood. If the kidneys are not working correctly, a mesothelioma patient could absorb far too much Alimta for their body to handle. Pemetrexed can cause serious toxicity in patients with impaired renal (kidney) function.
A New Way of Dosing Alimta for Mesothelioma
The dosing of Alimta for mesothelioma is based on body surface area (BSA). But the Dutch team says this dosing method is flawed.
“BSA-based dosing introduces large variability in exposure and may lead to (hemato)toxicity in patients with impaired renal function,” states the new report in the journal Lung Cancer.
To get around the problem, the team used a previously developed pharmacokinetic model. Pharmacokinetic modeling is a technique for predicting the absorption, distribution, metabolism and excretion of substances.
Researcher applied the model to two mesothelioma patients. One patient was on dialysis and the other had mild kidney impairment.
“Both patients had an exposure above target after the initial dose, but a proportional dose reduction resulted in a therapeutic exposure in both patients (185 and 166 mg·h/L, respectively), that was well-tolerated,” say the authors.
When the dose was adjusted, the dialysis patient cleared the pemetrexed from his system at a rate that was comparable to the general population.
The study concludes that pharmacokinetically-guided dosing makes Alimta for mesothelioma feasible, even in patients with renal impairment.
De Rouw, N, et al, “Pharmacokinetically-guided dosing of pemetrexed in a patient with renal impairment and a patient requiring hemodialysis”, April 2019. Lung Cancer, pp. 156-158, https://www.lungcancerjournal.info/article/S0169-5002(19)30305-8/fulltext