[Intrathecal methotrexate in breast cancer meningeal carcinomatosis - Experience with a new administration schedule]

Bull Cancer. 2016 May;103(5):444-54. doi: 10.1016/j.bulcan.2016.02.002. Epub 2016 Mar 15.
[Article in French]

Abstract

Methotrexate represents the standard intrathecal treatment of breast cancer meningeal carcinomatosis. However, its optimal schedule remains undefined. The aim of the present study was to evaluate results obtained with the methotrexate schedule used in Saint-Louis hospital (Paris). Patients followed in Saint-Louis hospital for breast cancer and who received intrathecal methotrexate were included in this retrospective monocentric study. Intrathecal treatment received contained methotrexate 12 mg/day (days: 1-5) and then 15 mg/week until progression or toxicity. Between 2003 and 2015, 41 patients were included. Primitive tumours were RH+/HER2-, HER2+ and triple-negative in respectively 66%, 14%, 5% and 15% of patients, 22% of them had meningeal carcinomatosis as metastatic disease initial manifestation. Objective response rate was 54%, median overall survival was 4.0 mois [CI 95%: 3-7.3] and 1-year survival rate was 15.2% (11.4%, 50% et 0% in RH+/HER2-, HER2+ and triple-negative subgroups; HR=0.45 [0.21-0.97] between HER2+ and RH+/HER2-). In univariate analysis, prognostic factors were brain involvement (p=0.049), initial cerebrospinal fluid protein level (p=0.0002) and concomitant systemic treatment received (p=0.049). This intrathecal methotrexate schedule demonstrates a similar median overall survival as the one obtained with a dose-dense schedule and an improved quality of life. Nevertheless, as the objective response and 1-year survival rates are slightly inferior, a dose-dense schedule remains still preferred in HER2+ patients or in those harboring a mainly meningeal progression.

Keywords: Breast cancer; Cancer du sein; Intrathecal methotrexate; Meningeal carcinomatosis; Méningite carcinomateuse; Méthotrexate intrathécal.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Arachnoiditis / chemically induced
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Clinical Protocols
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Spinal
  • Meningeal Carcinomatosis / drug therapy*
  • Meningeal Carcinomatosis / etiology
  • Meningeal Carcinomatosis / mortality
  • Meningeal Carcinomatosis / secondary*
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Middle Aged
  • Paris
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Time Factors
  • Triple Negative Breast Neoplasms / chemistry
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antimetabolites, Antineoplastic
  • Methotrexate