title: Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis.
abstract: HER2-positive status is associated with increased risk of central nervous system (CNS) metastases in breast cancer patients. Leptomeningeal carcinomatosis (LMC) represents a rare but disastrous manifestation of metastatic breast cancer (MBC) with limited treatment options and poor prognosis. Several case reports of intrathecal (i.t.) trastuzumab in the treatment of LCM were published so far. Usually, i.t. trastuzumab was administered in monotherapy or in combination with metothrexate. Herein, we report for the first time two patients with metastatic breast cancer and leptomeningeal carcinomatosis treated by intrathecal methotrexate (15 mg total dose) and cytarabine (24 mg total dose) with escalating dose of trastuzumab. We observed that up to 100 mg of trastuzumab can be safely administered intratecally with i.t. metothrexate and cytarabine. Both patients achieved good control of leptomeningeal disease for 13.5 and 6 months without significant toxicity. We suggest that i.t. trastuzumab with cytarabine and metothrexate is associated with promising benefit and warrant further investigation.
authors.affiliation: Department of Medical Oncology, School of Medicine, Comenius University, Klenova 1, 833 10 Bratislava, Slovak Republic. misomego@gmail.com
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sycova-Mila
authors.forename: Jana
authors.initials: J
authors.lastname: Obertova
authors.forename: Jan
authors.initials: J
authors.lastname: Rajec
authors.forename: Stefania
authors.initials: S
authors.lastname: Liskova
authors.forename: Patrik
authors.initials: P
authors.lastname: Palacka
authors.forename: Stefan
authors.initials: S
authors.lastname: Porsok
authors.forename: Jozef
authors.initials: J
authors.lastname: Mardiak
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007278:Injections, Spinal; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D055756:Meningeal Carcinomatosis / Q000188:drug therapy* / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D007166:Immunosuppressive Agents; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab