Diminished expression of interleukin-2 receptors in vivo after prior chemotherapy in advanced cancer patients receiving recombinant interleukin-2.
In a phase I/II dose escalation study performed at our institution, a total of 14 advanced metastatic cancer patients received between 4 and 16 weeks of subcutaneous recombinant interleukin-2. Doses were escalated at weekly intervals, starting at 1.8 million IU/m2/day up to a maximum dose of 14.4 million U/m2 daily. When comparing patients with (n = 4) and without (n = 7) prior chemotherapy on day 0 (i.e., before rIL-2), both patient groups exhibited Tac IL-2 receptor (CD25) positive peripheral blood lymphocytes at equal levels of positivity (8%). In contrast, 4-week systemic treatment with subcutaneous rIL-2 at escalating dose levels revealed a significant difference in the up-regulation by interleukin-2 of CD25 cell surface receptor. Thus, after 4 consecutive weeks of treatment, patients without previous chemotherapy showed a mean CD25 positivity of peripheral blood lymphocytes at 38%, as compared with 22% in patients who did receive prior chemotherapy (p less than 0.05). These data suggest that chemotherapy pretreatment may have a significant effect on biological response to rIL-2 in vivo.
Atzpodien
J
J
Department of Hematology, M.H.H. University Medical Center, Hannover, Germany.
Körfer
A
A
Hadam
M
M
Schomburg
A
A
Menzel
T
T
Dallmann
I
I
Poliwoda
H
H
Kirchner
H
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000139:chemically induced*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D007155:Immunologic Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins