Treatment of Neoplastic Meningitis With Intrathecal 9-Nitro-camptothecin

概要

論文の詳細を見る
The topoisomerase I inhibitor, 9-nitro-camptothecin (9NC), is highly tumoricidal against glioblastoma multiforme (GBM) in vitro. However, systemic administration of 9NC has not shown the expected efficacy in clinical trials. This failure may be due to the rapid hydrolysis of 9NC in plasma from the active form to the inactive and myelosuppressive form in the presence of human albumin at physiologic pH. Concurrent treatment with anticonvulsants and dexamethasone, drugs indispensable for the supportive therapy of patients with GBM, has also been shown to decrease plasma concentrations of these drugs. Intrathecal drug delivery circumvents the blood-brain barrier and minimizes systemic toxicity. Intrathecal delivery of 9NC may also have the more specific advantage of significantly reducing the hydrolysis of 9NC that occurs after systemic delivery due to the more favorable pH and reduced albumin content in cerebrospinal fluid. The present study evaluated the toxicity and efficacy of intrathecal delivery of 9NC in an athymic rat model of neoplastic meningitis. Toxicity tests showed that 0.3μmol (5000μM), 0.03μmol (500μM), 0.003μmol (50μM), or 0.0003μmol (5μM) of 9NC administered intrathecally to the athymic rats caused no evidence of clinical or histological toxicity. Intrathecal administration of 0.3μmol (5000μM) of 9NC twice a week for three doses to athymic rats with neoplastic meningitis induced by the GBM cell line, U87MG⊿EGFR, resulted in a 26% increase of median survival compared to the control group (p<0.005). These results suggest that intrathecal treatment with 9NC may be useful for patients with GBM neoplastic meningitis.
社団法人日本脳神経外科学会の論文
2006-10-15

Treatment of Neoplastic Meningitis With Intrathecal 9-Nitro-camptothecin

スポンサーリンク

概要

著者

関連論文

スポンサーリンク