A. Lindemann et al., SERUM CYTOKINE LEVELS IN CANCER-PATIENTS TREATED WITH DIFFERENT SCHEDULES OF ULTRA-LOW-DOSE INTERLEUKIN-2, Journal of immunotherapy with emphasis on tumor immunology, 15(3), 1994, pp. 225-230
Citations number
24
Categorie Soggetti
Immunology,Oncology,"Medicine, Research & Experimental
Interleukin-2 (IL-2) induces secondary cytokines in vivo that may medi
ate antitumor effects as well as toxicity. The course and quantity of
this in vivo reaction may depend on scheduling of IL-2 due to changes
in responsiveness of the respective producer cells. This was evaluated
in a phase-Ib study with ultra-low-dose IL-2 at 0.9 and 4.5 MIU/m(2)
administered once daily subcutaneously either once weekly (4 doses, st
ratum I), three times a week every other day (9 doses, stratum II), or
five times a week every other week (10 doses, stratum III). Twenty-ei
ght patients with advanced cancer were randomly assigned to the six tr
eatment groups. Serum levels of IL-2, secondary cytokines, and soluble
receptors were significantly increased after a single dose of 0.9 MIU
/m(2) s.c. demonstrating systemic efficacy. Baseline levels and native
responsiveness were recovered after a 1-week treatment-free interval
in stratum I patients with the exception of sCD8 that was still increa
sed although readily inducible at that time. Stratum II patients exhib
ited a prolonged and possibly continuous elevation of all serum parame
ters studied. Values did not increase beyond the 2nd week of therapy a
nd even decreased with respect to sCD8 and neopterin. A sequential mod
e of administration (stratum III) may obviate some of these adaptive m
echanisms as evidenced from a progressive increase of neopterin and sC
D8 levels after the second treatment cycle, although induction of sTNF
RI was saturable under these conditions. Thus, scheduling of IL-2 prof
oundly affects in vivo responses as evidenced from cytokine and solubl
e receptor serum levels. These data may be important for the design of
IL-2 studies with respect to the induction of specific biological end
points.