Pre-operative Immunoprophylaxis with Interleukin-2 may Improve Prognosis in Radical Surgery for Colorectal Cancer Stage B-C

Abstract

Cancer-associated immunodeficiency is seriously worsened by surgical trauma. Short-term pre-operative interleukin-2 (IL-2) administration abolished post-operative immunodeficiency. The effects of a pre-operative IL-2 immunotherapy on the prognosis of colorectal cancer patients (Dukes' stages B and C), undergoing radical surgery, are reported. The study included, after post-operative stratification, 86 consecutive patients with colorectal cancer Dukes' stage B (57) and C (29), undergoing radical laparotomic surgery, randomised to be treated pre-operatively, with or without a short-term course of subcutaneous (s.c.) IL-2 immunotherapy. Human recombinant IL-2 was given s.c. at 6×10⁶ I.U. twice daily pre-operatively for 3 consecutive days. Surgery was performed 36 hours after the last IL-2 injection. Dukes' C patients of both groups received standard adjuvant chemotherapy consisting of 5-FU plus folates and radiotherapy for rectal cancer patients. After a median follow-up of 54 months (range 18-86), the progression rate was significantly lower in patients pre-treated with IL-2 than in controls: 9/42 (21.4%) IL-2 group vs. 19/44 (43.1%) controls, (p<0.03). The positive effect of immunotherapy was detected both in the Dukes' B group, with 5/29 (17%) progression in the IL-2 group vs. 9/28 (32%) in controls, and Dukes' C patients with 4/13 (30%) vs. 10/16 (62%). This study shows that a 3-day pre-operative course of IL-2 immunotherapy may improve prognosis in patients with colorectal cancer at Dukes' stages B and C, as previously demonstrated in patients with more advanced disease. Therefore, the early activation of the antineoplastic immune system in the first post-operative days following a presurgical activation with IL-2 may counteract the growth of minimal residual disease and prevent late disease progression.