Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha (IFN) in operable renal cell cancer (RCC). A phase III, randomized, multicenter, independent trial of the Italian Oncology Group for Clinical Research (GOIRC)

Abstract

Listen

Translate article

LBA5028 Background: For pts with non-metastatic RCC, no standard adjuvant treatment exists. Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting. Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation of the immune system with no relevant toxicity. Methods: From July1994 to March 2006, surgically treated RCC pts were randomized to the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle of s.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm × 1 d 3,4,5) + IFN (1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for the first 2 years and every 6 months for the remaining 3 years. Each patient received 12 cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age <75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T > 2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and no autoimmune disease. Based on a planned sample size of 320 pts, the trial was designed to have a 80% power to detect a 15% improvement in 5-year survival. Results: A total of 310 pts were randomized: 157 on arm A, 153 on arm B. Pts characteristics were well balanced between the two arms. At a median follow-up of 52 months, 77 pts relapsed: 35 in arm A and 42 in arm B. In the first 5 years of observation, disease free survival (DFS) curves were similar in the two arms, but diverged thereafter. DFS at 5 and 10 years was 0.73 and 0.73 in arm A vs 0.73 and 0.60 in arm B with an estimated Hazard Ratio (HR) of 0.84 (95% CI: 0.54–1.33 p=0.47). Efficacy of IT was more evident in patients with good PS (HR 0.78; 0.47–1.30 p=0.35); age<60 yrs (HR 0.61; 0.31–1.19 p=0.15), and low tumor grade (HR 0.70; 0.38–1.27 p=0.24). As for overall survival, 59 deaths were observed with no differences between the two arms. Toxicity was mild and limited to WHO grade 1 or 2 in the majority of cases. Conclusions: Low-dose adjuvant IL2+IFN is feasible in RCC and seems to reduce the risk of recurrence after 5 years from diagnosis. Follow-up update is still ongoing. No significant financial relationships to disclose.