A successful compartmental approach for the treatment of breast cancer brain metastases.
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.
['Nguyen|Thuy T|TT|', 'Angeli|Eurydice|E|', 'Darrouzain|François|F|', 'Nguyen|Quang T|QT|', 'Desvignes|Céline|C|', 'Rigal|Marthe|M|', 'Nevine|Osman|O|', 'Nicolas|Patrick|P|', 'Le|Quang V|QV|', 'Winterman|Sabine|S|', 'Pailler|Marie-Christine|MC|', 'Zelek|Laurent|L|', 'Paintaud|Gilles|G|', 'Janin|Anne|A|', 'Bousquet|Guilhem|G|']
D000328:Adult D000971:Antineoplastic Combined Chemotherapy Protocols D001812:Blood-Brain Barrier D001932:Brain Neoplasms D001943:Breast Neoplasms D002945:Cisplatin D005260:Female D006801:Humans D007262:Infusions, Intravenous D007278:Injections, Spinal D008279:Magnetic Resonance Imaging D018719:Receptor, ErbB-2 D000068878:Trastuzumab D016896:Treatment Outcome
HER2-overexpressing breast cancer Intrathecal trastuzumab Cerebrospinal fluid Brain metastasis Intrathecal methotrexate