Immunotherapeutic alternatives in superficial bladder cancer. Interferon, interleukin-2, and keyhole-limpet hemocyanin.

Interleukin-2, IFNs, and TNF are biologic response modifiers that are part of an intricate network of interacting cytokines released during an immune response. Lack of sufficient endogenous cytokine activity secondary to the immunosuppressive effects of tumor growth may be overcome by direct, local application of biologic response modifiers or immunostimulants such as BCG or KLH. Bacillus Calmette-Guérin remains the most effective immunotherapeutic agent for superficial transitional-cell carcinoma. Although the mechanism of action is unknown, the weight of evidence suggests that local cytokine release is involved in the effector pathway. Recent data have shown that the local application of new single-agent immunotherapies can have an effect on superficial transitional-cell carcinoma and CIS similar to that of chemotherapeutic agents and nearly identical to that of BCG. But, unlike the situation with chemotherapy or BCG, these effects are attended by minimal or no toxicity. Chemotherapy and BCG failures have also shown responses to direct instillation of cytokines. Further understanding of the exact mechanism of action of these agents and of their interaction should lead to the optimal antitumor regimen with the least toxicity. Determining the degree of host immunoresponsiveness and which combination of cytokines or immunotherapeutic or chemotherapeutic agents is most effective for a specific tumor type is the challenge for the future.