Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients

Background and Objectives: Low count of total and T helper lymphocytes pred icts a poor prognosis in cancer patients and surgical trauma can worsen can cer-related immunodeficiency. Aim of this phase 113 study is to verify toxi city and biological effects of interleukin-2 (IL-2) at 9 million IU/day sub cutaneously (sc.) administered one, two or three preoperative days in patie nts with gastric cancer undergoing radical surgery. Methods: Absolute value of total and T-helper (CD4) lymphocytes were measur ed at baseline and at 7th, 14th, and 50th postoperative days in 12 gastric cancer patients, who preoperatively received IL-2 at 9 million IU/day sc. a s follows: group A (4 pts) 1-day; group B (4 pts) 2-days; group C (4 pts) 3 -days administration. T and total lymphocytes count were recorded and retro spectively analyzed in a historical control-group of 22 consecutive patient s, age and stage-matched. Results: Toxicity consisted of fever grade I. In group A (1 day) T helper l ymphocytes count decreased at 7th and at 14th postoperative day; in group B (2 days) and group C (3 days) no decrease of neither total nor T helper ly mphocyte count occurred postoperatively, whereas in the historical group th ese parameters decreased significantly postoperatively and recovered only a t 50th day. Conclusions: Two- and three-day schedules of sc. IL-2 preoperative administ ration at 9 million IU/daily prevented postoperative lymphocytopenia, where as one-day administration did not. Since the IL-2 dose was so tolerable. th at it could be given safety as outpatient, based on the previous results on survival observed in colorectal cancer patients with 3-days schedule we su ggest that a 3-day schedule of Interleukin-2 as outpatient preoperative tre atment seems advisable for further studies in gastric cancer patients. (C) 2001 Wiley-Liss, Inc.