Anti‐tumor effect of combined treatment with thymosin alpha 1 and interleukin‐2 after 5‐fluorouracil in liver metastases from colorectal cancer in rats

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Abstract
We studied the effect of combined chemo‐immunotherapy, 5‐FU followed by thymosin α1 (Tα1) and interleukin‐2 (IL‐2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2‐dimethylhydraiine‐induced 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 S‐FU/Tαl/IL‐2. S‐FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. Tα1 and IL‐2 were administered for 4 days and repeated after 11 days. Combined chemo‐immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra‐hepatic spread. 5‐FU/Tαl/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 immunode‐pressed rats and enhanced PBMC cytotoxic activity against the OHD/K12autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases.

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