Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.
OBJECTIVE
To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days.


METHODS
Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle.


RESULTS
The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease.


CONCLUSIONS
DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.
Glantz
M J
MJ
Department of Medicine, Brown University School of Medicine, Providence, RI, USA.
LaFollette
S
S
Jaeckle
K A
KA
Shapiro
W
W
Swinnen
L
L
Rozental
J R
JR
Phuphanich
S
S
Rogers
L R
LR
Gutheil
J C
JC
Batchelor
T
T
Lyter
D
D
Chamberlain
M
M
Maria
B L
BL
Schiffer
C
C
Bashir
R
R
Thomas
D
D
Cowens
W
W
Howell
S B
SB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008223:Lymphoma / Q000150:complications*; D008297:Male; D008582:Meningitis, Aseptic / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D003561:Cytarabine