Perioperative Immunmodulation beim Nierenzellkarzinom - eine Standortbestimmung

Böhm, Malte; Klatte, T.; Allhoff, E. P.

doi:10.1055/s-2003-42008

Aktuel Urol

2003

DOI: 10.1055/s-2003-42008

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Perioperative Immunmodulation beim Nierenzellkarzinom - eine Standortbestimmung

Malte Böhm

T. Klatte²,

E. P. Allhoff³

Abstract: Surgery and immunotherapy are the mainstay in the treatment of renal cell carcinoma. Surgery, however, is associated with considerable perioperative immunodysfunction. This immunodysfunction can be modulated by pretreatment with Interleukin-2 (IL-2), which appears to prolong tumour-specific survival. Perioperative immunomodulation could help close the therapeutic gap between neoadjuvant and adjuvant immunotherapy. This article reviews recent literature and presents original data of 63 patients.

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Cited by 2 publications

References 26 publications

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

Klatte

Ittenson

et al. 2006

Br J Cancer

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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 ¼ 60) and perioperative immunomonitoring without immunomodulation (control group; n ¼ 60). Patients from the IL-2 group received four doses of 10 Â 10 6 IU m À2 twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 Â 10 6 IU m À2 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 factorb1, 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 ¼ 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.

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

Klatte

Ittenson

et al. 2006

Br J Cancer

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Pretreatment with Interferon-a2a Modulates Perioperative Immunodysfunction in Patients with Renal Cell Carcinoma

Klatte¹,

Ittenson

Röhl³

et al. 2008

Onkologie

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Introduction: Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Here, we report on the effect of preoperative treatment with interferon-α2a (IFN-α2a). Materials and Methods: 30 patients with a renal tumour received preoperative IFN-α2a for 6 days beginning 1 week before nephrectomy, 30 did not. Parameters of cellular and humoral immunity were measured in venous blood at various intervals using flow cytometry and ELISA. Endpoints included effects on immune parameters, toxicity, and survival. Results: Toxicity was grade 1 in 52%, 2 in 30%, and 3 in 4%. During IFN-α2a administration, leukocytes, monocytes, granulocytes, B-cell marker CD19, activation markers, CD4+CD25+ regulatory T-cells, and vascular endothelial growth factor (VEGF) dropped significantly, but no difference was observed in T-cell and natural killer (NK)-cell markers, and IL-10. Postoperatively, T-cell and activation markers decreased in both groups, but CD4, CD28, IL-6, IL-10, and HLA-DR alterations were significantly less accentuated in patients who had been treated with IFN-α2a. After a median follow-up of 23 months, survival did not differ between the groups (p = 0.54). Conclusions: Perioperative immunodysfunction can be modulated by preoperative administration of IFN- α2a. IFN-α2a decreased the level of VEGF and CD4+CD25+ regulatory T-cells implicating a potential combination with tyrosine kinase inhibitors and vaccines.

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Perioperative Immunmodulation beim Nierenzellkarzinom - eine Standortbestimmung

Cited by 2 publications

References 26 publications

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

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

Pretreatment with Interferon-a2a Modulates Perioperative Immunodysfunction in Patients with Renal Cell Carcinoma

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