M. Rosener et al., TOLERANCE AND CEREBROSPINAL-FLUID PHARMACOKINETICS OF INTRATHECALLY ADMINISTERED HUMAN NATURAL INTERLEUKIN-2 - A PHASE-I TRIAL, European cytokine network, 4(3), 1993, pp. 189-195
Recombinant interleukin-2 (rIL-2) is at present widely applied in the
immunotherapy of various advanced cancers. As a number of side effects
following the administration of rIL-2, either alone or in combination
with lymphokine-activated killer (LAK-) cells, have been reported, a
preparation of human leukocyte-derived and fully glycosylated interleu
kin-2 was used in the present study. We have recently demonstrated in
cats that this natural IL-2 (nIL-2) is well tolerated and that the dis
tribution and elimination half-lifes following intrathecal (i.th.) app
lication are considerably longer than those after intravenous (i.v.) i
njection. To determine whether these long half-lifes and the good tole
rance of i.th. given nIL-2 are also found in man, four patients with m
eningeosis neoplastica received repeated injections of human nIL-2 i.t
h.. Cerebrospinal fluid samples were drawn at different time intervals
from either the lateral ventricle or lumbar subarachnoid space. The d
oses of nIL-2 ranged from 2 x 10(4) to 4 x 10(5) IU per injection. Onl
y minor side effects were noted in one patient. The half-lifes for dis
tribution and elimination of i.th. given nIL-2 ranged between 0.5 - 1.
7 hours and 4.9 - 14.4 hours respectively. A linear relationship exist
s between the i.th. dose of nIL-2 and the area under the cerebrospinal
fluid activity time profile curve.