Levamisole as a therapeutic agent for colorectal carcinoma

The prognosis of colon cancer patients found to have lymph node involvement at the time of primary surgical resection is guarded, with an overall 5-year survival rate of approximately 33%. The compound 5-fluorouracil (5-FU), an antimetabolite with some clinical activity in patients with metastatic colorectal cancer, has failed to produce a clinically meaningful impact when used as a single agent in the adjuvant setting. Recently, the results of a definitive intergroup trial (Moertel et al., N. Engl. J. Med. 322: 352-358, 1990) confirmed the results of a smaller trial that had suggested a therapeutic benefit from the combination of 5-FU and levamisole (Lev), an anthelminthic with immunomodulatory properties; these results have defined a new standard of care for patients with node-positive colon cancer. In this review, the rationale for using Lev as an adjuvant to 5-FU therapy in colon cancer, the immunologic effects of Lev in preclinical and clinical studies, and the results of clinical trials will be discussed.