title: Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions.
abstract: Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea. silver2sky@hanmail.net.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea. drleekh@gmail.com.|Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea. drleekh@gmail.com.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, Seoul 03080, Korea. wook616@hanmail.net.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea. bhumsuk@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea. bhumsuk@snu.ac.kr.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D018951:Antigens, CD20 / Q000737:chemistry / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D055756:Meningeal Carcinomatosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000639:trends*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069283:Rituximab / Q000627:therapeutic use
chemical_list: D018951:Antigens, CD20; D000964:Antimetabolites, Antineoplastic; D000069283:Rituximab; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D008727:Methotrexate
keywords: breast cancer; leptomeningeal carcinomatosis; lung cancer; molecular targeted agent