van den Bent M J
NeuroOncology Unit, Daniel den Hoed Cancer Center/Erasmus University Medical Center, PO Box 5201, 3008AE Rotterdam, The Netherlands.
Eur J Cancer. 2003 Oct;39(15):2114-20. doi: 10.1016/s0959-8049(03)00577-x.
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.
尽管人们普遍认为脑转移瘤对化疗有抵抗性，但恶性肿瘤的中枢神经系统转移灶对化疗的敏感性与身体其他部位的转移灶相同。这是因为在增强对比的脑转移瘤中血脑屏障被破坏，不会限制对化疗的反应。因此，原发肿瘤的反应率。对于脑转移瘤， upfront化疗而非放疗应基于原发肿瘤对所用方案的化疗敏感性，而不是所用药物是否能穿透完整血脑屏障的问题。对于有脑转移且仅有轻微神经体征和症状、并有身体其他部位转移灶系统化疗指征的患者，可进行一线化疗。相比之下，中枢神经系统微转移灶可能隐藏在完整的屏障之后，这在可通过化疗治愈的患者（如小细胞肺癌患者）中可能具有临床相关性。细胞色素P450 3A4诱导型抗癫痫药物，如苯妥英、卡马西平和苯巴比妥，可能会显著增加许多化疗药物（如CPT11和紫杉醇）以及许多新型生物制剂（如许多酪氨酸激酶抑制剂）的代谢。在需要使用通过细胞色素P450代谢的药物进行化疗的患者中，应避免使用这些抗癫痫药物。
