title: Neurological and cytological response as potential early predictors of time-to-progression and overall survival in patients with leptomeningeal carcinomatosis treated with intrathecal liposomal cytarabine: a retrospective cohort study.
abstract: Interesting neurological and cytological response rates after intrathecal (i.t) liposomal cytarabine have been observed in patients with leptomeningeal carcinomatosis (LMC) from solid tumors. However, the potential use of those responses as early predictors of time-to-progression (TTP) and overall survival (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t liposomal cytarabine under compassionate drug use were retrospectively studied. All patients received i.t treatment every 2 weeks during induction and every 4 weeks during maintenance periods. Neurological and cytological responses were assessed before every liposomal cytarabine cycle. Most of the patients were female (17/27) diagnosed with breast cancer (15/27). A complete neurological response was seen among 11 % of the patients; partial response in 22 % of the patients; stable disease in 30 % of the patients and progressive disease in 37 % of them. Cytological assessment was available in 11/27 patients showing a 26 % complete response rate. The median time to neurological and cytological response was 15 days and 14 days, respectively. Patients showing a combined neurological and cytological response showed a significantly longer median TTP (122 vs. 3 days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing both neurological and cytological progression. No grade 4 toxicities were recorded. According to these preliminary results, early neurological and cytological responses may be further studied as early predictors of TTP and OS in patients receiving i.t liposomal cytarabine for LMC.
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, c/Pío XII 36, 31008, Pamplona, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fusco
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañón
authors.forename: Omar E
authors.initials: OE
authors.lastname: Carranza
authors.forename: Leire
authors.initials: L
authors.lastname: Zubiri
authors.forename: Patricia
authors.initials: P
authors.lastname: Martín
authors.forename: Jaime
authors.initials: J
authors.lastname: Espinós
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Marta
authors.initials: M
authors.lastname: Santisteban
authors.forename: José M
authors.initials: JM
authors.lastname: Aramendía
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects*; D003581:Cytodiagnosis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes / Q000627:therapeutic use; D008297:Male; D055756:Meningeal Carcinomatosis / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009422:Nervous System Diseases / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D003561:Cytarabine
references.citation: Cancer. 2009 Jan 15;115(2):381-9
references.pmid: 19109820
references.citation: Hematol Oncol Clin North Am. 2012 Aug;26(4):917-31
references.pmid: 22794290
references.citation: J Thorac Oncol. 2012 Feb;7(2):382-5
references.pmid: 22089116
references.citation: Expert Opin Pharmacother. 2005 Jun;6(7):1115-25
references.pmid: 15957966
references.citation: Arch Neurol. 2009 Jan;66(1):74-8
references.pmid: 19139302
references.citation: Neuro Oncol. 2012 Jan;14(1):43-52
references.pmid: 21993441
references.citation: Lancet Oncol. 2010 Sep;11(9):871-9
references.pmid: 20598636
references.citation: J Clin Oncol. 1987 Oct;5(10):1655-62
references.pmid: 3309199
references.citation: J Neurooncol. 2007 Aug;84(1):57-62
references.pmid: 17310266
references.citation: Clin Transl Oncol. 2012 Apr;14(4):280-6
references.pmid: 22484635
references.citation: Lung Cancer. 2012 Jun;76(3):387-92
references.pmid: 22186628
references.citation: J Neurooncol. 2013 May;113(1):83-92
references.pmid: 23456656
references.citation: Clin Cancer Res. 1999 Nov;5(11):3394-402
references.pmid: 10589750
references.citation: Arch Pathol Lab Med. 2000 May;124(5):759-61
references.pmid: 10782164
references.citation: J Neurooncol. 2007 Jan;81(2):201-8
references.pmid: 16941075
references.citation: Jpn J Clin Oncol. 2003 Dec;33(12):608-12
references.pmid: 14769837
references.citation: J Neurooncol. 2002 May;57(3):231-9
references.pmid: 12125986