Abstract:
Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.
摘要:
治疗中枢神经系统(CNS)的转移性恶性肿瘤具有挑战性,因为许多药物无法穿过血脑屏障(BBB)。将鞘内(IT)药物直接施用到脑脊液(CSF)中是克服该问题的策略。Thiotepa具有有效的CNS渗透,但由于对其功效和潜在的全身毒性的担忧,其受欢迎程度在过去的二十年中有所下降。这篇综述评估了ITthiotepa在血液系统恶性肿瘤和非中枢神经系统实体瘤伴软脑膜疾病转移(LMD)中使用的可用证据。我们的搜索表明,由于实体器官恶性肿瘤,ITthiotepa是血液系统恶性肿瘤和LMD的合理选择。这表明ITthiotepa在二线或三线治疗中具有潜在作用,或者在药物短缺和其他药物不良反应的情况下具有替代作用。未来的研究应该集中在严格的比较试验上,以确定其在中枢神经系统导向化疗的演变中的决定性作用。