ANTITUMOR EFFECT OF COMBINED TREATMENT WITH THYMOSIN ALPHA-1 AND INTERLEUKIN-2 AFTER 5-FLUOROURACIL IN LIVER METASTASES FROM COLORECTAL-CANCER IN RATS

We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin alpha I (T alpha I) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2-dimethylhydrazine-inducedd colon adenocarcinoma) in syngeneic BDIX rats. The presence of liver metastases was checked by laparotomy 14 days after tumor-cell injection. Evaluable rats were assigned randomly to 5 experimental groups designated as control, 5-FU, IL-2, 5-FU/IL-2 and 5-FU/T alpha I/IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. T alpha I and IL-2 were administered for 4 days and repeated after 11 days. Combined chemo-immunotherapy was shown both the significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/T alpha I/IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-blood-mononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/K12 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases. (C) 1994 Wiley-Liss, Inc.