Two Cases of Leptomeningeal Metastases from Lung Adenocarcinoma Which Progressed During Gefitinib Therapy but Responded to Erlotinib

We present two patients with leptomeningeal metastases (LM) from lung adenocarcinoma that progressed or newly developed, respectively, during gefitinib therapy which had exhibited substantial antitumor effects on widespread lesions. In both cases, a switch to erlotinib therapy brought about long-lasting dramatic symptomatic improvement and markedly prolonged survival. The first patient is a 46-year-old female who presented with progressive headache and vomiting. Multiple pulmonary, hepatic and bone metastases immediately shrank in response to gefitinib. However, 1 month after completion of concurrent whole brain radiation, dizziness and urinary retention newly emerged, worsening the symptoms observed at presentation. Magnetic resonance imaging (MRI) demonstrated enlargement of ventricles and new gadolinium (Gd)-enhanced disseminated nodules on the surface of the cerebral cortex, suggesting the existence of uncontrollable LM. Sequential erlotinib therapy resulted in symptomatic improvement with a finding of regression of Gd-enhancement on MRI. The beneficial effect lasted for 10 months, though a follow-up brain MRI showed further enlarged ventricles. She finally died due to LM after surviving for 11 months under erlotinib treatment. The other patient is a 55-year-old female in whom headache and vomiting occurred while gefitinib therapy had maintained shrinkage of all pre-existing tumors in the thorax and bones. Brain MRI strongly suggested occurrence of LM with a finding of Gd-enhanced sulci. A switch to erlotinib therapy relieved the symptoms with disappearance of Gd-enhancement. However, the symptoms recurred with a finding of further enlargement of ventricles on brain MRI after 11 months. Finally, she died due to LM after surviving for 12 months under erlotinib treatment.