Breast Cancer Research and Treatment

, Volume 139, Issue 1, pp 13–22 | Cite as

Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis

  • Flora Zagouri
  • Theodoros N. Sergentanis
  • Rupert Bartsch
  • Anna S. Berghoff
  • Dimosthenis Chrysikos
  • Evandro de Azambuja
  • Meletios-Athanassios Dimopoulos
  • Matthias Preusser


Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38–66). The mean total dose was 399.8 mg (SD 325.4, range 35–1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55–1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06–1.37). Clinical improvement (HR 0.14, 95 % CI 0.02–0.91) and CSF response (HR 0.09, 95 % CI 0.01–0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC.


Breast cancer Intrathecal Trastuzumab Meningeal carcinomatosis HER2-positive 



FZ is receiving a research grant from HeSMO. Matthias Preusser and Rupert Bartsch have received unrestricted research grants and lecture honoraria by Roche. Evandro de Azambuja and Flora Zagouri have received lecture honoraria and travel expenses form Roche.

Conflict of interest

The authors have declared no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Flora Zagouri
    • 1
    • 2
  • Theodoros N. Sergentanis
    • 1
  • Rupert Bartsch
    • 2
  • Anna S. Berghoff
    • 2
  • Dimosthenis Chrysikos
    • 4
  • Evandro de Azambuja
    • 3
  • Meletios-Athanassios Dimopoulos
    • 1
  • Matthias Preusser
    • 2
  1. 1.Department of Clinical Therapeutics, Alexandra Hospital, Medical SchoolUniversity of AthensAthensGreece
  2. 2.Department of Medicine I/Division of Oncology, Comprehensive Cancer Center ViennaMedical University of ViennaViennaAustria
  3. 3.Medical Oncology DepartmentInstut Jules Bordet and L’Université Libre de Bruxelles (U.L.B)BrusselsBelgium
  4. 4.1st Propaedeutic Surgical Department, Hippocrateio HospitalUniversity of AthensAthensGreece

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