The role of chemotherapy in brain metastases.
Despite the widely held belief of the resistance to chemotherapy of brain metastases, central nervous system metastases of a malignancy are equally sensitive to chemotherapy as its metastases elsewhere in the body. This is due to the fact that the blood-brain barrier is disrupted in contrast enhancing brain metastases, and does not limit the response to chemotherapy. Therefore, the response rate of the primary tumour. Up-front chemotherapeutic treatment instead of radiotherapy of brain metastases should therefore be based on the chemosensitivity of the primary tumor to the used regimen, and not on the question whether the used agent penetrates an intact blood-brain barrier. First-line chemotherapy for brain metastases or with only minor neurological signs and symptoms, and who have an indication for systematic chemotherapy for metastases elsewhere in the body. In contrast, central nervous system micrometastases may hide behind an intact barrier, and this may be clinically relevant in patients that can be cured with chemotherapy (like in small cell lung cancer). Cytochrome P450 3A4 inducing anti-epileptic drugs like phenytoin, carbamazepine and phenobarbital may significantly increase the metabolism of many chemotherapeutic agents like CPT11 and paclitaxel (but also of newer biological agents like many tyrosine kinase inhibitors). These anti-epileptic drugs should be avoided in patients requiring chemotherapy with agents metabolised through the cytochrome P450.
van den Bent
M J
MJ
NeuroOncology Unit, Daniel den Hoed Cancer Center/Erasmus University Medical Center, PO Box 5201, 3008AE Rotterdam, The Netherlands. m.vandenbent@erasmusmc.nl
D000927:Anticonvulsants / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D000077204:Temozolomide
D000927:Anticonvulsants; D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide