Key Takeaways
- Pemetrexed is an FDA-approved chemotherapy drug used to treat mesothelioma when surgery is not an option. It was approved in 2004 and must be administered in combination with cisplatin.
- Pemetrexed works by mimicking folic acid — a molecule the body uses for rapid cell growth. By binding to folic acid receptors, pemetrexed blocks the signal that drives fast-growing cancer cells, slowing tumor growth.
- A 2005 randomized study showed that pemetrexed combined with cisplatin improved median survival to 12.1 months, compared to 9.3 months with cisplatin alone.
- In clinical trials, nearly 50% of pleural mesothelioma patients had a partial response to pemetrexed, and one-third had stable disease — meaning the cancer stopped progressing.
- When combined with carboplatin (a different platinum-based drug), pemetrexed showed a 32% response rate in a phase I study.
- Pemetrexed-cisplatin remains the standard first-line chemotherapy for mesothelioma patients who are not candidates for surgery.
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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Frequently Asked Questions
What is pemetrexed and how does it treat mesothelioma?
Pemetrexed is an antifolate chemotherapy drug — meaning it mimics the molecular structure of folic acid, a naturally occurring substance the body uses for rapid cell growth. When pemetrexed binds to folic acid receptors, it blocks the real folic acid from doing its job, which slows or stops the rapid proliferation of cancer cells. Because mesothelioma grows in fast-dividing tissues, pemetrexed is especially effective at curbing tumor growth.
Why is pemetrexed combined with cisplatin?
The FDA approved pemetrexed in 2004 specifically for use in combination with cisplatin — not as a standalone drug. Cisplatin is a platinum-based molecule that interferes with cancer cell growth through a different biological mechanism than pemetrexed. When used together, the two drugs attack cancer cells through two separate pathways simultaneously, making the combination significantly more effective than either drug alone. A randomized study confirmed this, showing median survival of 12.1 months with the combination versus 9.3 months with cisplatin alone.
How effective is pemetrexed for treating mesothelioma?
Clinical research has shown promising results:
- Nearly 50% of pleural mesothelioma patients had a partial response to pemetrexed treatment
- One-third of patients achieved stable disease — meaning the cancer stopped progressing
- When combined with cisplatin, median survival improved from 9.3 months to 12.1 months
- A phase I study combining pemetrexed with carboplatin showed a 32% response rate
Pemetrexed-cisplatin remains the standard first-line chemotherapy for mesothelioma patients who are not candidates for surgery.
When is pemetrexed used instead of surgery?
Pemetrexed-cisplatin chemotherapy is typically used when surgery is not a viable option — either because the cancer is too advanced (unresectable), the tumor’s location makes surgical removal impractical, or the patient’s overall health does not allow for a major surgical procedure. It may also be used before surgery (neoadjuvant) to shrink tumors, or after surgery (adjuvant) to target remaining cancer cells.
What is the difference between cisplatin and carboplatin?
Both cisplatin and carboplatin are platinum-based chemotherapy drugs that interfere with cancer cell growth, but they differ in their side effect profiles and potency. Cisplatin is generally considered more effective but carries more severe side effects, particularly kidney toxicity and nausea. Carboplatin tends to be better tolerated with fewer side effects. When pemetrexed was combined with carboplatin in a phase I study, it produced a 32% response rate in mesothelioma patients, offering an alternative for patients who cannot tolerate cisplatin.
Are there newer treatments that work alongside or beyond pemetrexed?
Yes. While pemetrexed-cisplatin remains the chemotherapy standard, newer treatment options have emerged. The CheckMate 743 trial showed that a combination of two immunotherapy drugs — ipilimumab and nivolumab — improved overall survival compared to pemetrexed-cisplatin in previously untreated patients. Other emerging options include Tumor Treating Fields (NovoTTF) and ongoing clinical trials exploring immunotherapy combinations. Your oncologist can help determine whether chemotherapy, immunotherapy, or a combination is most appropriate for your situation.
What should I do if I’ve been diagnosed with mesothelioma and want to understand my treatment options?
If you or a loved one has been diagnosed with mesothelioma or another asbestos-related disease, understanding the full range of available treatments — including chemotherapy, immunotherapy, surgery, and clinical trials — is an important step. For information about your legal options and to request a free Pennsylvania Mesothelioma Information Guide, call (800) 505-6000 or fill out our contact form.
