ABSTRACT
BACKGROUND: After initial response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM). To achieve longer survival, control of CNS metastases is important, but therapeutic options are limited for LM after failure of standard-dose EGFR-TKIs. METHODS: We retrospectively evaluated the efficacy and safety of high-dose erlotinib in EGFR-mutant non-small cell lung cancer (NSCLC) patients with refractory LM after failure of standard-dose EGFR-TKIs. Survivals from diagnosis of LM to death were compared in patients with or without high-dose erlotinib. RESULTS: Between January 2007 and April 2013, we identified 35 patients with EGFR-mutant NSCLC, complicated with LM, and 12 underwent high-dose erlotinib, while the other 23 received only standard-dose EGFR-TKIs. In patients receiving high-dose erlotinib, magnetic resonance imaging response was confirmed in 3 (30 %) of 10 evaluable patients. Median time to CNS progression was 2.3 months (95 % confidence interval [CI] 1.8-5.5 months). Performance status and neurological symptoms improved in 4 (33 %) of 12 and 6 (50 %) of 12 patients, respectively. No severe adverse events (≥grade 3) associated with high-dose erlotinib were observed. Median survival time from diagnosis of LM in patients with high-dose erlotinib was 6.2 months (95 % CI 2.5-8.5 months), and in those without 5.9 months (95 % CI 1.3-7.8 months) (p = 0.94). CONCLUSION: High-dose erlotinib suggested its efficacy and safety in some patients with refractory LM. It represents a potential therapeutic option against LM after failure of standard-dose EGFR-TKIs, especially to palliate LM-related neurological symptoms.
Subject(s)
Antineoplastic Agents/administration & dosage , ErbB Receptors/antagonists & inhibitors , Meningeal Carcinomatosis/chemically induced , Protein Kinase Inhibitors/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinazolines/administration & dosage , Quinazolines/adverse effects , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Erlotinib Hydrochloride , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Meningeal Carcinomatosis/genetics , Meningeal Carcinomatosis/metabolism , Middle Aged , Mutation/genetics , Retrospective Studies , Treatment OutcomeABSTRACT
Introducción. La carcinomatosis meníngea (CM) es una complicación rara de las neoplasias en estadios avanzados. El 5% de las neoplasiasse presentan como una CM. Clínicamente se manifiestan con diplopía, papiledema y/o déficit visual. Ante su sospecha es necesario la realización de una resonancia magnética nuclear y una punción lumbar para su diagnóstico. Caso clínico. Paciente de 54 años diagnosticado de adenocarcinoma de próstata con oscurecimientos visuales y papiledema como primera manifestación de una carcinomatosis meníngea. Discusión. Se discute como proceder ante un edema de papila bilateral secundario a hipertensión intracraneal. Conclusiones. Se resalta la importancia de considerar la posibilidad de invasión meníngea de una neoplasia, cuando nos encontramos un paciente con déficit neurológico y/o visual sin datos de infección o lesión ocupante de espacio (AU)
Introduction. Meningeal carcinomatosis (MC) is a rare complication of late-stage tumors. The 5% of the tumors are presented as a MC. Clinically it was manifested with diplopia, papilledema and / or visual deficits. MC is usually diagnosed by magnetic resonance imaging and cerebrospinal fluid analysis. Case report. A 54-year old man with prostate adenocarcinoma,presented to the emergency service with papilledema, and visual obscurations as first manifestation of meningeal carcinomatosis. Discussion. We discuss how to proceed before a bilateral papilledema due to intracranial hypertension. Conclusions. The importance of considering the possibility of a malignant meningeal invasion, when we find a patient with neurologicaland / or visual deficits without evidence of infection or space occupying lesion (AU)
