Mesothelioma patients undergoing chemotherapy treatment with pemetrexed (Alimta) may be able to avoid one of the more uncomfortable parts of the procedure thanks to information gained from a new Danish study.
Pharmacologists at the University of Copenhagen say the practice of draining so-called third-space fluid in patients undergoing pemetrexed-based chemotherapy may not be necessary. Third-space fluid is fluid that collects in body spaces not usually filled with fluid. In the case of patients with pleural mesothelioma or lung cancer, this fluid may collect in the space between the layers of the lung lining (pleura).
Managing the toxicity of powerful chemotherapy drugs like pemetrexed is a delicate process. Pleural draining or evacuation is often recommended prior to a new dose of chemotherapy as a way to ensure that accumulated pemetrexed in this space does not trigger severe toxic reactions. But new data suggests that it may be time to reconsider this recommendation which was based on reactions to a different drug.
“This is based upon the recommendations for methotrexate and not directly to any specific findings relating to pemetrexed,” says the study’s lead author Per Hartvig Honoré. Dr. Honoré says the draining recommendation had been extended to pemetrexed largely because it is an analog of methotrexate.
To test accumulation of pemetrexed in pleural fluid, the team extracted fluid from 8 non-small cell lung cancer patients who had been treated with pemetrexed and a platinum drug, the same drug combination used to treat pleural mesothelioma. After evaluating ten samples, the researchers found that concentrations of pemetrexed in the pleura after treatment were only half of what they were in plasma samples taken at the same time, suggesting that the drug clears from pleural fluid relatively quickly.“Pemetrexed is not likely to accumulate in the pleural fluid and evacuation of fluid might not be necessary,” concludes the Danish study.
Draining of the pleural fluid can be painful and can increase the risk of infections in patients with mesothelioma and other cancers. While draining of excessive pleural fluid may still be necessary to alleviate certain mesothelioma symptoms, the University of Copenhagen researchers say their finding suggests that it does not necessarily have to happen as a matter of course in those on pemetrexed.
A 2010 German study on pemetrexed accumulation in third-space fluid in mesothelioma patients produced similar results.
Honore, PH et al, “Third-space fluid distribution of pemetrexed in non-small cell lung cancer patients”, June 17, 2014, Cancer Chemotherapy and Pharmacology, Epub ahead of print,
Dickgreber, NJ et al, “Pemetrexed safety and pharmacokinetics in patients with third-space fluid”, May 15, 2010, Clinical Cancer Research, pp. 2872-2880.