Levamisole as an immunoadjuvant: phase I study and application in breast cancer.

A phase I study of levamisole in patients with cancer was undertaken to determine its therapeutic dose range, side effects, limiting toxicity, and influence on immune function. Simultaneously, a group of patients receiving adjuvant combination chemotherapy for carcinoma of the breast were entered in a randomized study to observe whether levamisole was capable of overcoming the immunodepressive effects of cytotoxic drugs. In the phase I trial the doses used ranged from 65 to 410 mg/m2. The maximum tolerated dose was 358 mg/m2. Side effects were generally low in intensity and related to the gastrointestinal and central nervous systems; the limiting toxic effect was intractable nausea. Significant changes in immune test values were noted in both acute and chronic trials. Alterations in immunoglobulin levels, complemented values, and numbers and types of lymphocytes and mitogenic responses to concanavalin A as well as specific mitogens were observed. In the randomized trial there was no difference between the chemoimmunotherapy and chemotherapy-alone groups.