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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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https://www.hal.inserm.fr/inserm-02528130
Contributor : Philippe Ratajczak <>
Submitted on : Wednesday, April 1, 2020 - 4:27:29 PM
Last modification on : Friday, April 3, 2020 - 1:52:39 AM

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Thuy Nguyen, Eurydice Angeli, François Darrouzain, Quang Nguyen, Celine Desvignes, et al.. A successful compartmental approach for the treatment of breast cancer brain metastases. Cancer Chemotherapy and Pharmacology, Springer Verlag, 2019, 83 (3), pp.573-580. ⟨10.1007/s00280-018-3752-z⟩. ⟨inserm-02528130⟩

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