Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed

Pemetrexed (PEM) is an antimetabolite drug that interferes with enzymes involved in DNA synthesis and also the folate-dependent metabolic processes necessary for DNA replication and homocysteine homeostasis. Continuation maintenance with PEM after induction therapy with PEM plus cisplatin has been the standard form of first-line chemotherapy for advanced non-squamous non-small cell lung cancer. The regimen has a low incidence of bone marrow suppression, and the incidences of anemia, leukopenia, neutropenia and thrombocytopenia exceeding grade 3 are less than 5%. Here we report a 68-year-old Japanese man with stage IIIB (cT4N3M0) lung adenocarcinoma who received 4 cycles of chemotherapy with PEM 500 mg/m² and cisplatin 75 mg/m² every three weeks, which resulted in a partial response, and then continued to receive maintenance PEM monotherapy. After 11 cycles of PEM maintenance therapy, the patient's platelet count decreased, and progressed to pancytopenia within two months. A bone marrow puncture revealed replacement with fatty marrow. As other diseases possibly responsible for pancytopenia were ruled out, we diagnosed the patient as having aplastic anemia. This is the first reported case of aplastic anemia to have occurred during PEM therapy. Clinicians should bear in mind that PEM can potentially trigger severe pancytopenia, including aplastic anemia.