TREATMENT OF LEPTOMENINGEAL METASTASIS WITH INTRAVENTRICULAR ADMINISTRATION OF DEPOT CYTARABINE (DTC 101) - A PHASE-I STUDY
TREATMENT OF LEPTOMENINGEAL METASTASIS WITH INTRAVENTRICULAR ADMINISTRATION OF DEPOT CYTARABINE (DTC 101) - A PHASE-I STUDY
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DOI：
10.1001/archneur.1993.00540030027009
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发表时间：
1993-03-01
影响因子：
--
通讯作者：
KIM, S
中科院分区：
文献类型：
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作者：
CHAMBERLAIN, MC;KHATIBI, S;KIM, S
Depo cytarabine (DTC 101 [formerly identified as Depo/Ara-C]) is a slow-releasing, depot formulation in which cytarabine is encapsulated within the aqueous compartments of microscopic (DepoFoam) particles. A phase I trial of DTC 101, given intraventricularly, was conducted in patients with leptomeningeal metastasis. Nine patients were given 1 to 7 cycles of DTC 1 01 in doses ranging from 25 to 1 25 mg that were administered via an Ommaya reservoir into the lateral ventricle. The dose-limiting toxic reaction was encephalopathy that occurred at the 125-mg dose level. All toxic episodes but one were transient and reversible, with the total duration of toxicity lasting from 1 to 7 days. The ventricular concentration of free cytarabine released from DTC 101 into cerebrospinal fluid decreased biexponentially with an initial half-life of 7.2 +/- 1.7 (+/- SEM) hours and a terminal half-life of 140 +/- 49 hours. The cerebrospinal fluid was cleared of malignant cells within 3 weeks of initial therapy in five of six cytologically evaluable patients. The duration of response ranged from 2 to more than 14 weeks, with a median of over 11 weeks. In conclusion, DTC 101 appears to be a pharmacologically attractive agent for use against leptomeningeal metastasis. The toxic episodes that occur with this therapy are well tolerated by patients.
