e14621 Background: primary and acquired resistance cause treatment failure to several agents. Recently it is emerging the role of immune surveillance in the control of tumor progression. The immune tolerance correlates with disease progression and FOXP3+ regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) play a relevant role in immunosuppression. Cyclophosphamide (C) and Fluorouracil (FU) seems to reduce these cell populations. Methods: Objective: safety, feasibility, pain control, activity and impact on immune system (Neutrophil/Lymphocyte (N/L), Platelet/L (P/L), Tregs %, Monocytes (M)(103/μL) count.Treatment: 1) C 300 mg/sqm +/- FU 500 mg/sqm day (d) 1, Interleukin-2 (IL-2) 18 MUI/sqm intravenous continuous infusion (i.v.c.i) d 3-5, 17-19 q 29 or 2) C 300 mg/sqm + FU 500 mg/sqm day d 1, IL-2 4.5 MUI subcutaneous (s.c) d 3-6, 17-20 q 29 for 2 cycles. Stable or responding patients (pts) continue therapy for three cycles. Results: from February 2014 to December 2016, 13/14 pts were treated. M/F:1/1. Median age was 68 years and median PS 1 (range 0-2). The primary tumor was bladder, liver, pancreas, neuroendocrine carcinoma and ovary in 2, melanoma, prostate, GIST and breast in 1 pt respectively. Sites of metastases were: lung in 4, liver in 9, lymph’nodes in 9, bone in 5 and spleen in 1 pt respectively. Previous therapy: 1- 2 in 6, ≥ 3 in 8. Six and 7 pts performed treatment 1, 2 respectively. Median number of cycles administered was 2 (range 1-3). Median basal and post-treatment N/L, P/L, M and Treg values were 2, 130, 0.49, 2,9% and 2, 94, 0.55, 10.5%. Pain improvement was obtained on 7/8 pts. The toxicity was manageable as for i.v.c.i as for s.c administration. In addition to universal capillary like syndrome, G3-4 toxicities were diarrhea, bleeding, anemia in 2, proteinuria in 1 pt respectively. Response: 3 PR (2 HCC, 1 pancreas), 2 SD, 4 PD, 5 unevaluable. The duration of response was 2+ and 3 months in 2 HCC pts and 8+ months in pancreatic pt. The crude median PFS and OS was 1 (range1-8+) and 2+ (range 1-18) months Conclusions: C- FU- IL-2 can be considered safe, feasible and meanly active in heavy pretreated pts. Except P/L, no reduction on Tregs, M counts and N/L was observed.