PURPOSE: Because there is a compelling need to develop new agents for intrathecal use, we investigated the safety, efficacy, and CSF pharmacokinetics of @entity29601 (AZQ) following intrathecal administration in @entity1 with refractory meningeal @entity5 . @entity1 AND METHODS: Thirty-nine @entity1 received 45 courses of intrathecal AZQ. Two schedules were studied; twice-weekly administration of a 1- or 2-mg dose and "concentration times time" (C x T) administration of 0.5 mg every 6 hours for three doses, administered once weekly. RESULTS: Dose-limiting @entity137 consisting of @entity10 , @entity390 , or @entity391 occurred in only three @entity1 and only at the 2-mg, twice weekly dose. The schedules of 1 mg twice-weekly and 0.5 mg every 6 hours for three doses were well tolerated. Thirty-seven courses were assessable for response. The overall response rate was 62%. Complete responses (CRs) occurred in 14 of 37 courses (38%) and partial responses (PRs) occurred in nine of 37 courses (24%). Among @entity1 with @entity693 , CRs were observed in 11 of 26 courses (42%) and PRs in nine of 26 courses (35%). There was no difference in response rate related to dose or schedule. The pharmacokinetic behavior of intrathecally administered AZQ was characterized by biexponential disappearance from ventricular CSF, with mean half-lives of 18.2 and 78.6 minutes. The mean clearance rate was 0.37 mL/min. CONCLUSION: Intrathecal AZQ is safe, well tolerated, and highly active against refractory meningeal @entity5 .

Phase I/II trial and pharmacokinetics of intrathecal XXXX in refractory meningeal @entity5 .

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignancies'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity29601 :: ('MESH:C029108', 'Chemical') :: ['diaziquone'] @entity693 :: ('MESH:D008581', 'Disease') :: ['meningeal leukemia'] @entity10 :: ('MESH:D006261', 'Disease') :: ['headache']
@entity29601 :: (MESH:C029108,Chemical) :: ['diaziquone']
