Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial.
We conducted a non-randomised controlled phase II trial to investigate the role of preoperative administration of interleukin-2 (IL-2) in patients with renal cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients were allocated alternately to the two study groups: perioperative immunomodulation with IL-2 (IL-2 group; n=60) and perioperative immunomonitoring without immunomodulation (control group; n=60). Patients from the IL-2 group received four doses of 10 x 10(6) IU m(-2) twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 x 10(6) IU m(-2) subcutaneously until a day before the operation. Parameters of cellular and humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34, as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist, transforming growth factor-beta1, and vascular endothelial growth factor) were measured in peripheral venous blood at various intervals. Interleukin-2-related toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period, T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and IL-10 increased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Median follow-up was 40 months. Tumour-specific survival in the IL-2 group and the control group was 98 vs 81% after 1 year and 86 vs 73% after 5 years (P=0.04). A similar effect was found for progression-free survival. We conclude that IL-2 can be safely administered in the perioperative period and modulates immunological parameters. However, to validate the survival data, a larger randomised phase III trial is needed.
Klatte
T
T
Department of Urology, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Ittenson
A
A
Röhl
F-W
FW
Ecke
M
M
Allhoff
E P
EP
Böhm
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D003248:Constipation / Q000139:chemically induced; D016207:Cytokines / Q000032:analysis; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D015703:Antigens, CD; D016207:Cytokines; D007155:Immunologic Factors; D007376:Interleukin-2