Combination Therapy with Bacillus Calmette-Guerin (BCG) and Interferon-alpha in Superficial Bladder Cancer Patients: Immune Effector Cell Function and Toxicity

Cho, Yong Hyun; Kim, Sae Woong; Kim, Jin Ho; Yoon, Moon Soo

Abstract

The aim of this study was to evaluate immune effector cell function and toxicity of adjuvant intravesical bacillus Calmette-Guerin(BCG) plus systemic interferon- alpha administration in 12 superficial bladder cancer patients received transurethral resection. 80mg Pasteur strain BCG was instilled into the bladder at 2 weeks after transurethral resection and carried out once a week for 6 weeks. 3 million units interferon-alpha 2b was injected subcutaneously at 2 weeks after transurethral resection and carried out 3 times a week during the period of BCG therapy. Natural killer cell activity, Helper T cell/Suppressor T cell (CD4/CD8) ratio and phagocytic activity were evaluated by flowcytometry and toxicity was graded according to WHO guidelines. The results were as follows: 1. Natural killer cell activity of interferon-alpha or BCG in combination with interferon-alpha treated group was significantly increased compared to control or BCG treated group, also the activity of those two groups was significantly correlated between pre and post treatment state. 2. CD4/CD8 ratio of interferon-alpha or BCG in combination with interferon-alpha treated group was significantly increased compared to control or BCG treated group, also the activities of those two groups were significantly correlated between pre and post treatment state. 3. No significant differences in phagocytic activity were seen between all experimental groups or pre and post treatment state. 4. The toxicity of BCG in combination with interferon-alpha treated group showed minor to moderate and self-limiting in majority of the patients. By the results of this study, it is supposed that intravesical BCG instillation in combination with subcutaneous Interferon-alpha injection increase systemic immune response without significant toxicity and may be effective in prophylaxis of tumor recurrence in the patients with superficial bladder cancer.