pemetrexed

Pemetrexed is a multitarget antifolate chemotherapy agent (brand name Alimta) used to treat malignant pleural mesothelioma and non-small cell lung cancer, particularly non-squamous types. It is usually given as an intravenous infusion and is commonly combined with platinum-based chemotherapy, although it can be used as monotherapy in some patients.

Mechanism of action

Pemetrexed inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This interference disrupts DNA and RNA synthesis, impairing tumor cell replication. Because of its antifolate activity, pemetrexed is administered with folic acid and vitamin B12 to reduce toxicity.

Dosing and administration

Standard regimens include pemetrexed 500 mg/m2 IV on day 1 of a 21-day cycle, with cisplatin 75 mg/m2 IV on day 1 in combination regimens for non-squamous NSCLC or malignant pleural mesothelioma. Pemetrexed can also be given as a single agent for patients who cannot receive platinum therapy. Dosing may be adjusted for renal impairment, and severe impairment may preclude use.

Supportive care and pretreatment

To reduce toxicity, patients receive folic acid supplementation and vitamin B12 before and during treatment. Folic acid is typically given daily starting about a week before the first dose, and vitamin B12 is given by injection every several weeks. Dexamethasone or another corticosteroid is used around each dose to lessen dermatologic reactions.

Adverse effects and precautions

Common adverse effects include fatigue, mucositis, rash, cytopenias, nausea, and liver enzyme elevations. Pemetrexed is contraindicated in pregnancy and requires careful use in renal impairment with appropriate dose adjustments. Patients are monitored with regular blood counts and kidney function tests, and drug interactions, including NSAIDs, are managed to minimize toxicity.