Patterns of folic acid activity in mesothelioma tumors can suggest whether a patient will respond to Alimta (pemetrexed), according to a study.
The patterns, which appear in biomarkers of the activity, could allow doctors to come up with other treatments for malignant pleural mesothelioma (MPM) patients who are unlikely to respond Alimta.
The study, “Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma,” was published in the journal Oncotarget.
Alimta is in a class of chemotherapy drugs called folate antimetabolites. It targets folic acid, or vitamin B9, a nutrient required for cell function and the growth of new cells, whether normal or cancerous. A downside of Alimta is that it causes serious side effects because it affects normal as well as cancer cells.
Researchers decided to examine the connection between folic acid phenotypes and Alimta. Phenotypes, also known as FAPs, are patterns of naturally occurring substances involved in cells’ folic acid activity.
The research team wanted to see which FAPs arose when Alimta was used to treat tumors samples. They also wanted to see whether particular FAPs were linked to tumor response to Alimta.
Researchers examined tissue samples from 56 MPM patients, most of whom had died. They classified the tumors as being in remission in response to Alimta, or progressing.
The team found that a phenotype they called FT was associated with tumor progression, meaning patients were not responding to Alimta. The finding indicated that doctors could use the presence of the phenotype to help decide whether to use Alimta to treat MPM patients.
“The FT phenotype was present in half of all progressive tumors, but absent in remissive cases, and can therefore support clinical decision making,” the authors wrote.
They also found a set of molecules known as FPGS/TYMS in phenotypes that identify a subgroup of responders to Alimta. More than half the group, which accounts for 18.6% of MPM patients, survived at least three years after treatment.
A major implication of the study is that, by identifying patients who do not respond to Alimta, doctors can spare them that treatment. This would prevent the patients from having to deal with the side effects of Alimta, and allow doctors to use treatment approaches that better suit the patients’ needs.
“Our results indicate that the balance between folic acid uptake, activation and metabolism plays a crucial role in response to pemetrexed-based chemotherapy and the prognosis of MPM patients. Implementing this marker profile in MPM stratification may help to individualize MPM-therapy more efficiently,” the authors concluded.