To the Editor,
Pemtrexed is a chemotherapy drug classified as a folate antimetabolite. It is chemically similar to methotrexate. Pemetrexed is approved for the treatment of mesothelioma, locally advanced and metastatic non-squamous non-small cell lung cancers [Citation1,Citation2]. We report a case of aseptic meningitis associated with the first intravenous (IV) administration of pemetrexed. A 54-year-old male with metastatic non-small cell lung cancer was treated with pemetrexed as second-line chemotherapy. He was started on folic acid and vitamin B12 a week prior to chemotherapy. After premedication with dexamethasone, pemetrexed infusion was given at a rate of 500 mg/m2 over a period of 10 minutes. The patient tolerated chemotherapy without any immediate side effects. One week later, the patient developed fever, headache, diffuse erythematous macular rash and altered mental state manifesting primarily as difficulty walking and a decreased level of consciousness that prompted a hospital admission. Computed tomography (CT)-scan of brain was negative for any acute intracranial process. Cerebral spinal fluid (CSF) analysis showed a white blood cell count (WBC) of 5/cumm, with 14% neutrophils. CSF glucose was 67 mg/dl (serum glucose 132 mg/dl) and protein level was 142 mg/l (normal 15–45 mg/dl). Both viral and bacterial studies were negative. Cytology results were also negative for malignant cells. The patient received antibiotics empirically, including ceftriaxone, vancomycin, ampicillin and acyclovir until viral and bacterial studies were reported. With supportive care, patient improved. He was discharged after two weeks.
Discussion
As an increasingly large number of patients are exposed to any new drug, uncommon but serious adverse drug reactions may come to light [Citation3]. To the best of our knowledge, this is the first case of pemetrexed induced aseptic meningitis. Drug induced aseptic meningitis is usually a diagnosis of exclusion. The pathophysiology of drug induced aseptic meningitis is not well understood [Citation4]. Two mechanisms have been proposed; direct meningeal irritation or a delayed hypersensitivity reaction. Aseptic meningitis presents with non-specific symptoms including: fever, headache, nausea with occasional photophobia and nuchal rigidity. Cerebral spinal fluid (CSF) studies vary widely in cases of aseptic meningitis. The CSF protein may be elevated but the glucose level is nearly always normal. The CSF WBC may range from normal to several thousands [Citation5]. In our patient, the temporal association, clinical and laboratory findings support the diagnosis of pemetrexed induced aseptic meningitis. Healthcare providers should be aware of this severe adverse event of pemetrexed.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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