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A Phase I Study

Marc C. Chamberlain, MD; Shirin Khatibi, DVM; Joseph C. Kim; Stephen B. Howell, MD; Etienne Chatelut, PhD; Sinil Kim, MD

Arch Neurol. 1993;50(3):261-264.

Abstract
• 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.

Author Affiliations
From the Departments of Neurosciences (Dr Chamberlain) and Medicine (Drs Khatibi, Howell, Chatelut, and Kim and Mr Kim), and the Cancer Center (Drs Chamberlain, Khatibi, Howell, Chatelut, and Kim and Mr Kim), University of California, San Diego.

Footnotes
Accepted for publication August 28, 1992.

Reprint requests to Department of Neurosciences, University of California, San Diego, 225 Dickinson St, San Diego, CA92103 (Dr Chamberlain).

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