Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study.
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.
Chamberlain
M C
MC
Department of Neurosciences, University of California, San Diego 92103.
Khatibi
S
S
Kim
J C
JC
Howell
S B
SB
Chatelut
E
E
Kim
S
S
D000328:Adult; D000368:Aged; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged
D003692:Delayed-Action Preparations; D003561:Cytarabine