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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

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

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. More... »

PAGES

573-580

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-018-3752-z

DOI

http://dx.doi.org/10.1007/s00280-018-3752-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111099666

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30610367


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    "description": "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.\nMETHODS: 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.\nRESULTS: 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\u00a0mg/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\u00a0mg/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\u00a0\u00b5mol/L at 2\u00a0h, and the concentrations remained above the theoretical therapeutic concentration. After 2\u00a0months of this drug combination, we obtained an excellent response on the brain metastases.\nCONCLUSION: 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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