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01-03-2019 | Metastasis | Original Article

A successful compartmental approach for the treatment of breast cancer brain metastases

Authors: Thuy T. Nguyen, Eurydice Angeli, François Darrouzain, Quang T. Nguyen, Céline Desvignes, Marthe Rigal, Osman Nevine, Patrick Nicolas, Quang V. Le, Sabine Winterman, Marie-Christine Pailler, Laurent Zelek, Gilles Paintaud, Anne Janin, Guilhem Bousquet

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2019

Abstract

Background

Brain metastases are challenging daily practice in oncology and remain a compartmental problem since most anti-cancer drugs do not cross the blood–brain barrier at relevant pharmacological concentrations.

Methods

In a young woman with HER2-overexpressing breast cancer resistant to standard treatments, at the time of brain metastases progression, a ventricular reservoir was implanted for intrathecal drug injections and detailed pharmacokinetic studies.

Results

A first association of intrathecal trastuzumab with intravenous cisplatin was offered to the patient. For trastuzumab, the mean cerebrospinal fluid trough concentration of 53.4 mg/L reached relevant levels, enabling the stabilization of the metastases. Adding intravenous cisplatin was not beneficial, since the cerebrospinal fluid exposure was almost undetectable under 0.08 mg/L. We then offered the patient an intrathecal combination of trastuzumab and methotrexate, because of their in vitro synergic cytotoxicity. The cerebrospinal fluid peak of methotrexate was 1037 µmol/L at 2 h, and the concentrations remained above the theoretical therapeutic concentration. After 2 months of this drug combination, we obtained an excellent response on the brain metastases.

Conclusion

Our preliminary study supports the interest of a compartmental approach through a direct administration of drugs into the cerebrospinal fluid for the treatment of breast cancer brain metastases.

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Title: A successful compartmental approach for the treatment of breast cancer brain metastases
Authors: Thuy T. Nguyen
Eurydice Angeli
François Darrouzain
Quang T. Nguyen
Céline Desvignes
Marthe Rigal
Osman Nevine
Patrick Nicolas
Quang V. Le
Sabine Winterman
Marie-Christine Pailler
Laurent Zelek
Gilles Paintaud
Anne Janin
Guilhem Bousquet
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keywords: Metastasis
Breast Cancer
Methotrexate
Methotrexate
Breast Cancer
Trastuzumab
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3752-z

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Abstract

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