Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer.

Abstract

Levamisole has been used in a wide array of clinical research and treatment settings over the past two decades, ranging from such diseases as helminthic infestations to various autoimmune diseases. Numerous preclinical evaluations and clinical trials with levamisole in the cancer arena have been sponsored by the National Cancer Institute and other agencies worldwide with the hopes of demonstrating anticancer activity. Trials in advanced breast cancer, lung cancer, colorectal cancer, melanoma, and lymphoproliferative diseases have generally been negative or inconclusive. However, there is some indication that levamisole may be useful by itself as an adjuvant therapy for resected melanoma; recently it has been shown to be effective in combination with fluorouracil (5-FU) as adjuvant therapy for tumor-node-metastasis (TNM) stage III (Dukes' C) colon carcinoma. In the aggregate, the past 20 years of clinical experience with levamisole has resulted in as many questions as answers. However, further testing of the anticancer activity of levamisole can be expected in clinical research trials over the next few years. Hopefully, these future trials will include studies of the mechanisms of action of this agent.

Post-operative levamisole may compromise early healing of experimental intestinal anastomoses

“…It may be that levamisole somehow stimulates collagenolysis. Levamisole has been reported to exert a broad range of immunomodulatory effects (Stevenson et al, 1991). It increases the chemotactic response of granulocytes, which cells accumulate immediately after wounding in the anastomotic area and are an important source for collagenolytic enzymes (Hasty et al, 1990).…”

“…Although a meta-analysis of its use shows only limited benefit (Buyse et al, 1988), 5-Fluorouracil (5-FU) remains the most effective single agent, and current research aims to improve its efficacy by combinations with other agents (Mayer, 1992;Kemeny et al, 1993). A number of studies have confirmed an improved therapeutic activity if 5-FU is combined with folinic acid (leucovorin) (Mayer, 1992;Kemeny et al, 1993), while the combination of 5-FU with levamisole also attracts considerable attention (Moertel et al, 1990;Stevenson et al, 1991). Major questions still to be resolved in the treatment of patients by surgery and subsequent adjuvant chemotherapy include, next to the choice of cytostatic agents, timing and route of administration.…”

Adjuvant 5-fluorouracil plus levamisole in colon cancer: the plot thickens?

“…In the UK, at least, levamisole has never been licensed for this application, and has now been withdrawn completely from all but clinical trial use (having been previously available on the named-patient basis at the discretion of oncologists). The claimed immunomodulator effects of levamisole have been difficult to substantiate (Stevenson et al, 1991) and appear more significant at dose levels higher than used in most clinical trials to date (Janik et al, 1993). Single-agent levamisole appears to have no anti-tumour activity (Moertel et al, 1990;Arnaud et al, 1989) in its own right, which is counterintuitive, at least if the example of breast cancer adjuvant therapy is considered, but does not rule out an effect of the combination by an as yet unexplained mechanism.…”

A Systematic Overview of Chemotherapy Effects in Colorectal Cancer

“…Levamisole is an antiparasitic drug without known antineoplastic properties (18), and has been used in cancer treatment without effect on survival when used alone (19). In the British trial, 141 patients with colon or rectal cancer Dukes' B and C were randomised to receive uorouracil » levamisole, uorouracil alone or no postoperative treatment (17).…”