Perioperative immunomodulation with interferon-alpha in patients with renal cell carcinoma: Early results of a controlled phase II trial

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14525 Background: Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Earlier, we presented evidence of a survival benefit in patients, who received perioperative immunomodulation with interleukin-2 (JCO 23 (16S):4601, 2005). Here, we report on the effect of interferon-alpha (IFN-α). Methods: Fifty-four consecutive patients, who underwent tumor nephrectomy, were enrolled into this prospective one stage phase II trial from June 2003 to May 2005. Patients were alternately assigned to the two study groups: 27 received immunomodulation with IFN-α (4 doses 9 million IU s.c a week before operation, followed by a daily dose of 3 million IU until a day before the operation), 27 did not. Parameters of immunity (differential blood count, CD3, CD4, CD8, CD16, CD19, CD28, CD56, HLA-DR, VEGF, IL-10) were measured in venous blood before and during IFN-α, one day before and immediately after the operation, and on the 1., 3., 5., and 10. postoperative day. The primary endpoint was tumor-specific survival. T-test, χ2-test and the log-rank test were used for statistical analysis. Results: The study groups did not differ with respect to age, sex, tumor stage and grade, histological type, operation time and technique. IFN-α related toxicity was WHO grade 0 (11%), 1 (59%), 2 (26%), and 3 (4%). During IFN-α administration leukocytes, CD19, HLA-DR and VEGF dropped significantly, while no difference was observed in T-cell and NK-cell markers, and IL-10. All patients showed postoperatively elevated leukocyte counts. T-cell and activation markers decreased, but CD3, CD4 and CD28 alterations were significantly less accentuated in patients who had been treated with IFN-α. Median follow-up was 14 months. The 1- and 2-year rates (±SE) of tumor-specific survival were 96% (±4%) and 83% (±12%) in the IFN-α group and 85% (±7%) and 85% (±7%) in the control group, respectively (p = 0.52). Also, no difference was seen in progression-free survival (p = 0.32). Conclusions: In this study with limited follow-up, perioperative IFN-α medication was not associated with a survival benefit, but was well tolerated. Interestingly, the decline in VEGF during administration suggests a role of IFN-α in the inhibition of angiogenesis. No significant financial relationships to disclose.