PHASE-II RANDOMIZED STUDY OF PREOPERATIVE IL-2 ADMINISTRATION IN OPERABLE NSCLC

Lymphocytopenia is a prognostic factor for shorter survival in advance d lung cancer and it is likely related to an interleukin-2 (IL-2) defi ciency occurring during cancer progression. Major surgery itself for c ancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevente d by preoperative administration of recombinant human (rhIL-2), indica ting that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) admini stered preoperatively is able to prevent the lymphocyte decrease occur ring after radical surgery in operable lung cancer. This phase II stud y included 40 patients with operable NSCLC screened as stage II or III A, randomized to receive rhIL-2, 9 000 000 IU subcutaneously twice dai ly for 3 days before surgery (treated group, 20 patients) or not (cont rol group, 20 patients). At baseline, there were no significant differ ences in total lymphocyte number and lymphocyte subsets (T-cell, T-hel per, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperativ ely the control group showed a decrease in total lymphocyte count, T-l ymphocyte count, T-helper cell number and CD4/CD8 ratio, significant a t the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and cont rol group values of total lymphocyte count, T-cells and T-helper cells . NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantl y over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control gr oup resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated p atients and 16/20 control patients were radically operated. After a 24 -month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 ra dically operated were disease-free; 8/20 control patients were alive a nd 4/16 radically operated were disease-free. Toxicity was mild to mod erate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administratio n of rhIL-2 is feasible and prevents lymphocyte decrease occurring pos toperatively after surgery for lung cancer. Further studies are requir ed to assess the impact on survival. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.