Tolerance and cerebrospinal fluid pharmacokinetics of intrathecally administered human natural interleukin-2: a phase I trial.
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 interleukin-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 distribution and elimination half-lifes following intrathecal (i.th.) application are considerably longer than those after intravenous (i.v.) injection. To determine whether these long half-lifes and the good tolerance of i.th. given nIL-2 are also found in man, four patients with meningeosis neoplastica received repeated injections of human nIL-2 i.th.. Cerebrospinal fluid samples were drawn at different time intervals from either the lateral ventricle or lumbar subarachnoid space. The doses of nIL-2 ranged from 2 x 10(4) to 4 x 10(5) IU per injection. Only minor side effects were noted in one patient. The half-lifes for distribution 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 exists between the i.th. dose of nIL-2 and the area under the cerebrospinal fluid activity time profile curve.
Rösener
M
M
Department of Neurology, University of Würzburg, Germany.
Schwuléra
U
U
Menke
G
G
Thrun
A
A
Lissner
R
R
Krauseneck
P
P
Bogdahn
U
U
Martin
R
R
D000328:Adult; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged
D007376:Interleukin-2