Key takeaways: When administered in conjunction with cisplatin, pemetrexed is an effective
drug to treat mesothelioma when surgery or other chemotherapeutic options are not available. It
works by mimicking the biological structure of folic acid, which is critical for the rapid
proliferation of cells (which is characteristic of mesothelioma and other cancers). When
pemetrexed binds to folic acid receptors, the typical effect of folic acid (to facilitate quick
cellular growth) is inhibited. This can assist in curbing the rapid growth of mesothelioma tumors,
and, by effect, increase a patient’s survival time.
Molecular Properties/Introduction
Pemetrexed is an antifolate, which is a class of drug that acts like folic acid (meaning that it has
the same molecular shape and binds to the same receptor as folic acid. This kind of action is
called antagonistic: a synthetic molecule with the same shape as an organic molecule binds to its
receptors so that the organic molecule cannot bind, and therefore, cannot effect any biological
changes.) Importantly, naturally-occurring folic acid plays a significant role in the proliferation
of fast-growing tissues, like bone marrow and skin. So, when an antifolate mimics folic acid (so
that the actual folic acid cannot bind to its respective receptors), the rapid proliferation of these
cells is slowed. For an aggressive cancer like mesothelioma, pemetrexed is a viable option for
slowing its growth, considering its location in quickly growing tissues.
Pemetrexed Treatment for Mesothelioma
The FDA approved the use of pemetrexed in 2004, so long as it was coupled with cisplatin.
Cisplatin is a platinum-based molecule that, like pemetrexed, interferes with cellular growth
(although through a different biological mechanism). A randomized study in 2005 found that
pemetrexed coupled with cisplatin significantly improved median survival time (12.1 months) as
compared to just a cisplatin treatment (9.3 months).
Another study found that “…nearly 50% of patients with pleural mesothelioma had a partial
response, and one third had stable disease (115). In a subsequent phase I study combining
pemetrexed with carboplatin in patients with this disease, there was a 32% response rate (116).”
Pemetrexed is exceptionally effective, and its use to curb the spread of other malignant cancers is
currently being explored.
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Sources:
Chattopadhyay, S., Moran, R. G., & Goldman, I. D. (2007). Pemetrexed: Biochemical and
cellular pharmacology, mechanisms, and clinical applications. Molecular Cancer
Therapeutics, 6(2), 404–417. https://doi.org/10.1158/1535-7163.MCT-06-0343
Hazarika, M., White, R. M., Booth, B. P., Wang, Y.-C., Ham, D. Y. L., Liang, C. Y.,
Rahman, A., Gobburu, J. V. S., Li, N., Sridhara, R., Morse, D. E., Lostritto, R., Garvey,
P., Johnson, J. R., & Pazdur, R. (2005). Pemetrexed in malignant pleural mesothelioma.
Clinical Cancer Research: An Official Journal of the American Association for Cancer
Research, 11(3), 982–992.
Visentin, M., Zhao, R., & Goldman, I. D. (2012). The Antifolates. Hematology/Oncology
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