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- Title
A successful compartmental approach for the treatment of breast cancer brain metastases.
- Authors
Nguyen, Thuy T.; Angeli, Eurydice; Darrouzain, François; Nguyen, Quang T.; Desvignes, Céline; Rigal, Marthe; Nevine, Osman; Nicolas, Patrick; Le, Quang V.; Winterman, Sabine; Pailler, Marie-Christine; Zelek, Laurent; Paintaud, Gilles; Janin, Anne; Bousquet, Guilhem
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
CEREBROSPINAL fluid; BREAST cancer; TRASTUZUMAB; METHOTREXATE; BRAIN metastasis
- Publication
Cancer Chemotherapy & Pharmacology, 2019, Vol 83, Issue 3, p573
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-018-3752-z