Topoisomerase I inhibitors in the treatment of primary CNS XXXX : an update on recent trends.

@entity1 @entity137 @entity2600 @entity5 @entity294 @entity11 @entity1398 @entity2903 @entity463
High grade primary @entity11 hold some of the worst prognoses of any @entity5 , with the vast majority of @entity1 dying within two years of diagnosis, even with aggressive modern treatments. Surgical resection and radiotherapy are cornerstones of treatment when possible. In spite of many years of research, only recently has management with chemotherapy been able to prolong survival in @entity1 with high grade @entity11 , albeit only modestly at best. Topoisomerase I (TOP1) inhibitors target an enzyme critical for DNA replication and cell-cycle progression; they cross the blood-brain barrier and have antitumor activity against @entity463 cells in vitro. The most frequently associated @entity137 are @entity1398 and @entity294 , but are often manageable. The two most used agents are @entity2600 and topotecan. Due to enhanced cytochrome CY3A4/5 enzyme activity, @entity2600 dose must be adjusted with concomitant enzyme-inducing antiepileptic drug usage; the data is less clear regarding the effects on topotecan. Clinical trials in @entity1 with recurrent @entity11 have evaluated TOP1 inhibitors as monotherapy and in combination with other agents. There is evidence for using topotecan with radiotherapy. @entity2600 has limited efficacy as monotherapy, but shows promise in combination with other agents, particularly @entity2903 and bevacizumab. Newer generation TOP1 inhibitors are currently being evaluated in phase I trials. TOP1 inhibitors show promising activity in @entity1 with primary CNS @entity5 and warrant further study.
