title: Concurrent intrathecal methotrexate and liposomal cytarabine for leptomeningeal metastasis from solid tumors: a retrospective cohort study.
abstract: Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of systemic cancer with limited survival. Randomized trials comparing single agent intrathecal methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. We hypothesized that combination intrathecal chemotherapy would be a safe and tolerable option in solid tumor LM. We conducted a retrospective cohort study of combination IT chemotherapy in solid tumor LM at a single institution between April 2010 and July 2012. In addition to therapies directed at active systemic disease, each subject received IT liposomal cytarabine plus IT methotrexate with dexamethasone premedication. Patient characteristics, survival outcomes and toxicities were determined by systematic chart review. Thirty subjects were treated during the study period. The most common cancer types were breast 15 (50 %), glioblastoma 6 (20 %), and lung 5 (17 %). Cytologic clearance was achieved in 6 (33 %). Median non-glioblastoma overall survival was 30.2 weeks (n = 18; range 3.9-73.4), and did not differ significantly by tumor type. Median time to neurologic progression was 7 weeks (n = 8; range 0.9-57), with 10 subjects (56 %) experiencing death from systemic disease without progression of LM. Age less than 60 was associated with longer overall survival (p = 0.01). Six (21 %) experienced grade III toxicities during treatment, most commonly meningitis 2 (7 %). Combination IT chemotherapy was feasible in this small retrospective cohort. Prospective evaluation is necessary to determine tolerability, the impact on quality of life and neurocognitive outcomes or any survival benefit when compared to single agent IT chemotherapy.
authors.affiliation: Department of Neurology, Lahey Hospital and Medical Center, 41 Mall Road, Burlington, MA, 01805, USA, brian.j.scott@lahey.org.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Scott
authors.forename: Vincent A
authors.initials: VA
authors.lastname: van Vugt
authors.forename: Toni
authors.initials: T
authors.lastname: Rush
authors.forename: Tiffany
authors.initials: T
authors.lastname: Brown
authors.forename: Clark C
authors.initials: CC
authors.lastname: Chen
authors.forename: Bob S
authors.initials: BS
authors.lastname: Carter
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.forename: Paul
authors.initials: P
authors.lastname: Fanta
authors.forename: Teresa
authors.initials: T
authors.lastname: Helsten
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Bazhenova
authors.forename: Barbara
authors.initials: B
authors.lastname: Parker
authors.forename: Sandeep
authors.initials: S
authors.lastname: Pingle
authors.forename: Marlon G
authors.initials: MG
authors.lastname: Saria
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Brown
authors.forename: David E
authors.initials: DE
authors.lastname: Piccioni
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005240:Feasibility Studies; D006801:Humans; D007278:Injections, Spinal; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008081:Liposomes; D008175:Lung Neoplasms / Q000473:pathology; D055756:Meningeal Carcinomatosis / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D003561:Cytarabine; D008727:Methotrexate