Phase-II randomized study of preoperative IL-2 administration in radically operable gastric cancer patients

BACKGROUND/AIMS: Surgery has appeared to induce lymphocytopenia and this decrease in host defenses during postoperative period could promote both the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. The aim of this study is to evaluate if the preoperative subcutaneous injection of IL-2 (interleukin-2) may be able to abrogate surgery-induced immunosuppression in radically operable gastric cancer and to assess its toxicity. METHODOLOGY: This phase II study included 39 consecutive patients with histologically proven gastric adenocarcinoma (M/F 26/13; mean age 68; range 48-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (20 patients) or surgery plus preoperative treatment with recombinant human IL-2 (19 patients). IL-2 was administered subcutaneously, at a dose of 9,000,000 IU, for three consecutive days, followed by surgery within 36 hours from IL-2 withdrawal. We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. Among the 22 patients evaluated in the control group 13 had a decreased of CD4 under 500 cells/mm3 (65%). Instead in the IL-2 group a significant increase was observed over the control group values of total lymphocytes and CD4 cells (14th ly total and CD4: IL-2 vs. control p