Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

• Published in: British journal of cancer 2006-11, Vol.95 (9), p.1167-1173
• Main Authors: Klatte, T, Ittenson, A, Röhl, F-W, Ecke, M, Allhoff, E P, Böhm, M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD - analysis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - surgery; Clinical Study; Combined Modality Therapy; Constipation - chemically induced; Cytokines - analysis; Diarrhea - chemically induced; Drug Administration Schedule; Drug Resistance; Epidemiology; Female; Follow-Up Studies; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Injections, Subcutaneous; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Interleukin-2 - therapeutic use; Kaplan-Meier Estimate; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Kidneys; Leukocyte Count; Leukocytes - cytology; Leukocytes - drug effects; Leukocytes - metabolism; Male; Medical sciences; Middle Aged; Molecular Medicine; Nephrology. Urinary tract diseases; Oncology; Treatment Outcome; Tumors; Tumors of the urinary system
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603391

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 × 10 6  IU m −2 twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 × 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- β 1, 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.