2012 Volume 52 Issue 2 Pages 242-247
Background. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), is effective against lung cancer positive for echinoderm microtubule-associated protein-like 4 (EML4)-ALK. However, cases with acquired resistance to crizotinib have also been reported. Pemetrexed (PEM), a multitargeted antifolate, has been widely used as not only first-line, but also as second-line and later chemotherapy of adenocarcinoma of the lung. Case. A 39-year-old woman received a diagnosis of adenocarcinoma of the lung with right hilar and mediastinal lymph node swelling, pericardial effusion, and multiple liver and bone metastases. Treatment with erlotinib and carboplatin+paclitaxel+bevacizumab was ineffective for her liver metastases. As the lung cancer was EML4-ALK-positive, the patient was treated with crizotinib as part of a clinical study, resulting in a partial response. However, 7 months later, treatment was terminated because the liver metastases had re-enlarged and brain metastases had appeared. Consequently, the patient received combined chemotherapy consisting of PEM and carboplatin as fourth-line treatment; she showed good response, with shrinkage of the liver metastases observed after 2 courses. After 4 courses of combined chemotherapy, treatment with PEM only was continued. Gamma-knife radiosurgery was performed for a single brain metastasis, which had been detected after the eighth course (26th week) of treatment. No re-enlargement of the liver metastases was seen, as confirmed by an abdominal CT scan after the 11th course (35th week); however, treatment was terminated after the 13th course (including 9 courses of PEM only) due to a diagnosis of carcinomatous meningitis during the 43rd week. Conclusion. In the present case, PEM showed long-term efficacy as fourth-line chemotherapy against EML4-ALK-positive adenocarcinoma of the lung after the development of acquired resistance to crizotinib. However, additional cases are needed to confirm the efficacy of PEM in patients with EML4-ALK-positive lung cancer.
