Tolerance and feasibility of perioperative treatment with interferon-alpha 2a in advanced cancers

Major surgery impairs the cellular immune response. In order to stimulate the immunological system during the perioperative period, we have studied the clinical and biological tolerance, and the immunological and histological effects of a perioperative treatment using progressive doses of Interferon-alpha 2a, from the third preoperative day (D-3) until the tenth postoperative day (D10).

Twenty-three patients undergoing a major surgical procedure for advanced cancer were included. The clinical and biological parameters evaluated were the body temperature and the blood cell counts. Immunological effects were evaluated by counting the total number of lymphocytes, lymphocyte subsets, natural killer cells (NK), and by analysis of the NK activity, and lymphokine-activated killer cell (LAK) assay.

Hyperthermia was the most toxic effect of Interferon-alpha but the overall toxicity was minor, even at the highest dose level. In the early postoperative period there was a significant decrease in total lymphocytes, and in most lymphocyte subset counts when compared with D-3. Overall NK and LAK activities significantly increased from D-3 to D-1 (p < 0.02). A postoperative decrease in NK activity was noted that was not significant when compared to pretherapeutic values, whereas a significant decrease in LAK activity did occur on D4 despite the interferon treatment (p < 0.03). Since we found a dose-dependent effect on some lymphocyte subsets, there was not a clear dose-dependent effect on NK and LAK activities.

Perioperative alpha 2a administration is a safe treatment in advanced cancer patients that may allow a postoperative preservation of NK activity and a destruction of potential circulating metastatic cells. Further studies are ongoing on perioperative immunotherapy in advanced cancer patients.