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Pemetrexed
General information
Pemetrexed (LY231514, MTA) is an antifolate congener. It is transported into cells by the reduced folate carrier and undergoes intracellular polyglutamylation, resulting in a persistent cytotoxic metabolite, which targeting several enzymes simultaneously, including dihydrofolate reductase, thymidylate synthase, GARFT, and AICARFT [ ].
Pemetrexed was approved as monotherapy for the treatment of advanced non-small cell lung cancer and in combination with cisplatin for the treatment of pleural mesothelioma [ , ]. Other indications include the treatment of lymphomas [ ] and solid tumors such as metastatic breast cancer [ ], inoperable and metastatic non-squamous cell lung cancer [ ], squamous cell carcinoma of the head and neck [ ], and mesothelioma [ ].
General adverse effects and adverse reactions
The most common adverse effects of pemetrexed are hematological (see below).
Grade 3 and 4 non-hematological adverse effects related to pemetrexed include stomatitis, diarrhea, vomiting, and skin reactions. However, the last can be significantly reduced by the prophylactic use of dexamethasone on the day before chemotherapy and for three subsequent days [ ].
Drug studies
Observational studies
Of 107 patients who had received at least four cycles of pemetrexed, 37 had adverse reactions that the authors described as “cutaneous adverse events” [ ]. There was conjunctivitis in 27, periorbital edema in 16, and limb edema in 14. Women were more commonly affected than men.
Organs and systems
Cardiovascular
Peripheral edema has occasionally been attributed to pemetrexed [ , ], and a systemic capillary leak syndrome, with pericardial and pleural effusions, widespread edema, and hypotension, occurred in a 74-year-old man [ ].
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