An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis.
Drugs currently available for intrathecal administration are cleared rapidly from the CSF. DepoCyt is a slow-release formulation of cytarabine that maintains cytotoxic concentrations of free cytarabine in the CSF for >14 days following a single injection. DepoCyt was administered to 110 patients with a diagnosis of neoplastic meningitis based on either a positive CSF cytology (76) or neurologic and CT or MRI scan findings sufficient to document neoplastic meningitis (34). Patients were treated with DepoCyt 50mg every 2 weeks for 1 month of induction therapy by either lumbar puncture (LP) or intraventricular (IVT) injection. Patients without neurologic progression were candidates to receive an additional 3 months of consolidation therapy. All patients received dexamethasone 4 mg BID on days 1-5 of each cycle. Median time to neurologic progression was 55 days; median overall survival was 95 days. Among the 76 patients with a positive CSF cytology at baseline, 70 were evaluable for response, and of this group 19 (27%) attained the criteria for response (cytologic response in the absence of neurologic progression). The most important adverse events were headache and arachnoiditis. When drug-related, these were largely low grade, transient, and reversible. Drug-related grade 3 headache occurred on 4% of cycles; grade 3 or 4 arachnoiditis occurred on 6% of cycles. No cumulative toxicity was observed. DepoCyt injected once every 2 weeks produced a response-rate comparable to that previously reported for methotrexate given twice a week. The once in every 2-week-dosing interval offers an advantage over conventional schedules (2-3 doses/week) used for other agents available for intrathecal injection.
Mayo Clinic, Jacksonville, FL, USA.
Kurt A
KA
Jaeckle
Tracy
T
Batchelor
Steven J
SJ
O'Day
Surasak
S
Phuphanich
Pamela
P
New
Glenn
G
Lesser
Allen
A
Cohn
Mark
M
Gilbert
Robert
R
Aiken
Deborah
D
Heros
Lisa
L
Rogers
Eric
E
Wong
Dorcas
D
Fulton
John C
JC
Gutheil
Said
S
Baidas
Julia M
JM
Kennedy
Warren
W
Mason
Paul
P
Moots
Christy
C
Russell
Lode J
LJ
Swinnen
Stephen B
SB
Howell
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D018450:Disease Progression; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D003561:Cytarabine