Chamberlain M C, Khatibi S, Kim J C, Howell S B, Chatelut E, Kim S
Department of Neurosciences, University of California, San Diego 92103.
Arch Neurol. 1993 Mar;50(3):261-4. doi: 10.1001/archneur.1993.00540030027009.
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 101 in doses ranging from 25 to 125 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.
阿糖胞苷长效注射剂（DTC 101 [以前称为Depo/Ara-C]）是一种缓释的长效制剂，其中阿糖胞苷被包裹在微小（DepoFoam）颗粒的水相隔室中。对患有软脑膜转移的患者进行了一项DTC 101脑室内给药的I期试验。9名患者接受了1至7个周期的DTC 101治疗，剂量范围为25至125毫克，通过奥马亚贮液器注入侧脑室。剂量限制性毒性反应是在125毫克剂量水平出现的脑病。除1例外，所有毒性发作均为短暂且可逆的，毒性总持续时间为1至7天。从DTC 101释放到脑脊液中的游离阿糖胞苷的脑室浓度呈双指数下降，初始半衰期为7.2 +/- 1.7（+/-标准误）小时，终末半衰期为140 +/- 49小时。在6例可进行细胞学评估的患者中，有5例在初始治疗后3周内脑脊液中的恶性细胞被清除。缓解持续时间为2至超过14周，中位数超过11周。总之，DTC 101似乎是一种用于治疗软脑膜转移的具有药理学吸引力的药物。这种治疗出现的毒性发作患者耐受性良好。
