**3. Immunotherapy IL2,IFα**

Two trials that used adjuvant IFN-α [32, 33] and one study that used adjuvant high-dose IL-2 (82) were negative for any benefit. The latter study was designed and powered to show an improvement in predicted 2-year DFS from 40% for the observation group to 70% for the treatment group. Despite full accrual 30% improvement in 2-year DFS could not be achieved which lead to early study closure.

Combination treatment with IFN-α and IL2 also failed to improve DFS in one trial [34].

The combination of cytokines with 5-fluorouracil (5-FU) also failed to improve DFS in the adjuvant setting [35, 36].

In one randomized adjuvant trial, triple combination therapy using IL-2, IFN-α, and5-FU was associated with significant toxicity which leads to 35% of the patients did not complete the study and also resulted in no benefit in DFS or OS [37].
