Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients.
OBJECTIVE
Low count of total and T helper lymphocytes predicts a poor prognosis in cancer patients and surgical trauma can worsen cancer-related immunodeficiency. Aim of this phase IB study is to verify toxicity and biological effects of interleukin-2 (IL-2) at 9 million IU/day subcutaneously (sc.) administered one, two or three preoperative days in patients with gastric cancer undergoing radical surgery.


METHODS
Absolute value of total and T-helper (CD4) lymphocytes were measured 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. as 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 retrospectively analyzed in a historical control-group of 22 consecutive patients, age and stage-matched.


RESULTS
Toxicity consisted of fever grade I. In group A (1 day) T helper lymphocytes 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 lymphocyte count occurred postoperatively, whereas in the historical group these parameters decreased significantly postoperatively and recovered only at 50th day.


CONCLUSIONS
Two- and three-day schedules of sc. IL-2 preoperative administration at 9 million IU/daily prevented postoperative lymphocytopenia, whereas one-day administration did not. Since the IL-2 dose was so tolerable, that it could be given safely as outpatient, based on the previous results on survival observed in colorectal cancer patients with 3-days schedule we suggest that a 3-day schedule of Interleukin-2 as outpatient preoperative treatment seems advisable for further studies in gastric cancer patients.
Cerea
K
K
1(st) General Surgery Department, II University of Milano-Bicocca, San Gerardo Hospital-Monza (Milano), Italy.
Romano
F
F
Bravo
A F
AF
Motta
V
V
Uggeri
F
F
Brivio
F
F
Fumagalli
L A
LA
Uggeri
F
F
D000230:Adenocarcinoma / Q000150:complications / Q000601:surgery*; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D013274:Stomach Neoplasms / Q000150:complications / Q000601:surgery*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007376:Interleukin-2