Antifolate

Antifolates are a class of chemotherapy drugs that block the body's ability to use folate (vitamin B9), a nutrient cells need to build and repair DNA. Because cancer cells divide rapidly and depend heavily on folate pathways, antifolates starve those cells of the building blocks they need to multiply. The most relevant antifolate for mesothelioma patients is pemetrexed (brand name Alimta), usually given with cisplatin or carboplatin as first-line chemotherapy.

Origin

The term combines "anti-" (against) with "folate" (a B-vitamin). Antifolate cancer therapy began in 1948, when Sidney Farber used aminopterin to achieve the first temporary remissions in children with leukemia. Pemetrexed was approved by the FDA in 2004 specifically for malignant pleural mesothelioma in combination with cisplatin, based on the Vogelzang phase III trial that showed a survival benefit over cisplatin alone.

Significance in Asbestos Context

For most patients with malignant pleural mesothelioma, pemetrexed plus a platinum drug (cisplatin or carboplatin) has been the backbone of first-line chemotherapy for nearly two decades and remains one of the few regimens with proven survival benefit in this disease. Since 2020, the immunotherapy combination of nivolumab plus ipilimumab has become an alternative first-line option, particularly for non-epithelioid (sarcomatoid or biphasic) tumors, while pemetrexed-based chemotherapy continues to be widely used for epithelioid disease and as a second-line option after immunotherapy. The choice between antifolate chemotherapy, immunotherapy, or a combination depends on your tumor's histologic subtype, your overall health, kidney function, and personal preferences about side effects, all worth discussing in detail with your oncologist. The fact that a patient requires antifolate chemotherapy also documents the severity of the diagnosis in medical records that may later support a legal claim.

Example Sentence

After her pleural mesothelioma diagnosis, she began an antifolate-based regimen of pemetrexed and cisplatin, with folic acid and vitamin B12 supplementation started a week before her first infusion.

Related Terms

Pemetrexed (Alimta), Cisplatin, Chemotherapy, Mesothelioma, Immunotherapy, First-Line Treatment

Notes

• Before your first pemetrexed infusion, confirm that your oncologist has prescribed daily oral folic acid and scheduled vitamin B12 injections every 9 weeks. These are mandatory, not optional, and dramatically reduce the risk of severe blood-count drops and mouth sores. A corticosteroid such as dexamethasone is also given around each infusion to prevent skin rash.
• Ask your oncologist which platinum drug they are pairing with pemetrexed. Cisplatin has the strongest evidence but is harder on the kidneys and hearing; carboplatin is often substituted for older patients or those with reduced kidney function.
• Ask specifically how your tumor's histologic subtype (epithelioid, sarcomatoid, or biphasic) factors into the choice between antifolate chemotherapy and immunotherapy. Non-epithelioid subtypes often respond better to immunotherapy, while epithelioid disease historically responds well to pemetrexed.
• Keep copies of all infusion records, pharmacy receipts, supplementation logs, and documentation of side effects or hospitalizations. These records support both your ongoing care and any asbestos trust or lawsuit claim for medical expenses.
• If you are considering a clinical trial, ask whether prior pemetrexed exposure would exclude you from enrollment, since some trials require patients to be treatment-naïve or to have had specific prior regimens.