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

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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Acknowledgements

We would like to thank Mrs. A. Swaine for revising the English language. We would also like to thank Dr. S. Szyldergemajn for his helpful advices. The study was supported by INSERM and University Paris 7.

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Authors and Affiliations

Authors

Contributions

TTN conceived and designed the study, provided the study material or patient, collected and assembled the data, provided data analysis and interpretation, and drafted the manuscript. EA provided data analysis and interpretation. FD provided data analysis and interpretation, provided the study material, provided administrative support and located financial support. QTN provided the study material and provided administrative support. CD provided the study material and provided administrative support. MR provided the study material and provided administrative support. ON provided the study material and provided administrative support. PN provided the study material, provided administrative support, provided data analysis and interpretation. QVL provided the study material and provided administrative support. SW provided the study material and provided administrative support. M-CP collected and assembled the data. LZ collected and assembled the data. GP provided the study material, provided administrative support, provided data analysis and interpretation. AJ conceived and designed the study, provided the study material, provided administrative support, provided data analysis and interpretation, drafted the manuscript and located financial support. GB conceived and designed the study, provided the study material, provided administrative support, collected and assembled the data, provided data analysis and interpretation, drafted the manuscript and located financial support.

Corresponding authors

Correspondence to Anne Janin or Guilhem Bousquet.

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The authors declare no conflict of interest.

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Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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Nguyen, T.T., Angeli, E., Darrouzain, F. et al. A successful compartmental approach for the treatment of breast cancer brain metastases. Cancer Chemother Pharmacol 83, 573–580 (2019). https://doi.org/10.1007/s00280-018-3752-z

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  • DOI: https://doi.org/10.1007/s00280-018-3752-z

Keywords

  • HER2-overexpressing breast cancer
  • Brain metastasis
  • Intrathecal trastuzumab
  • Intrathecal methotrexate
  • Cerebrospinal fluid