title: Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa.
abstract: Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.
authors.affiliation: Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005, Paris, France, aurelie_comte@yahoo.fr.
authors.forename: A
authors.initials: A
authors.lastname: Comte
authors.forename: W
authors.initials: W
authors.lastname: Jdid
authors.forename: M N
authors.initials: MN
authors.lastname: Guilhaume
authors.forename: I
authors.initials: I
authors.lastname: Kriegel
authors.forename: S
authors.initials: S
authors.lastname: Piperno-Neumann
authors.forename: V
authors.initials: V
authors.lastname: Dieras
authors.forename: T
authors.initials: T
authors.lastname: Dorval
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: P H
authors.initials: PH
authors.lastname: Cottu
authors.forename: L
authors.initials: L
authors.lastname: Mignot
authors.forename: F C
authors.initials: FC
authors.lastname: Bidard
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D055756:Meningeal Carcinomatosis / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D008875:Middle Aged; D060787:Neoplasm Grading; D009422:Nervous System Diseases / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013852:Thiotepa / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013852:Thiotepa
references.citation: J Neurooncol. 1998 Jun-Jul;38(2-3):245-52
references.pmid: 9696379
references.citation: Semin Oncol. 2009 Aug;36(4 Suppl 2):S46-54
references.pmid: 19660683
references.citation: J Clin Oncol. 1993 Mar;11(3):561-9
references.pmid: 8445432
references.citation: Cancer. 1982 Feb 15;49(4):759-72
references.pmid: 6895713
references.citation: Cancer. 1996 Apr 1;77(7):1315-23
references.pmid: 8608509
references.citation: N Engl J Med. 1973 Oct 11;289(15):770-3
references.pmid: 4517004
references.citation: Lancet Oncol. 2010 Sep;11(9):871-9
references.pmid: 20598636
references.citation: J Neurooncol. 2012 Aug;109(1):143-8
references.pmid: 22539243
references.citation: Ann Oncol. 2010 Nov;21(11):2183-2187
references.pmid: 20430906
references.citation: Neurology. 1983 Dec;33(12):1565-72
references.pmid: 6685829
references.citation: Cancer. 1976 Oct;38(4):1471-5
references.pmid: 825215
references.citation: J Clin Oncol. 1986 Jan;4(1):68-73
references.pmid: 3079822
references.citation: Ann Oncol. 2011 Feb;22(2):480-2
references.pmid: 21177280
references.citation: Cancer Treat Rep. 1977 Aug;61(5):885-7
references.pmid: 408003
references.citation: J Clin Oncol. 1987 Oct;5(10):1655-62
references.pmid: 3309199
references.citation: Oncologist. 2008 Sep;13(9):967-77
references.pmid: 18776058
references.citation: Clin Cancer Res. 1999 Nov;5(11):3394-402
references.pmid: 10589750
references.citation: J Support Oncol. 2012 Mar-Apr;10(2):45-53
references.pmid: 22005214
references.citation: Cancer. 1982 Jul 15;50(2):219-22
references.pmid: 6177395