Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Ergamisol (Janssen-Cilag)
50 mg tablets
Indication: colonic cancer
The combination of levamisole and fluorouracil, which was discussed in Australian Prescriber in 19921,
has now been approved for use after surgical resection of cancer of the colon.
Levamisole is active against helminths, but also modulates the immune system, particularly when the immune response is impaired. Although the drug has little effect on its own, adjuvant treatment with fluorouracil improves survival in patients with advanced colonic cancer. Patients with stage III colon cancer were entered into a randomised controlled trial within 5 weeks of surgery. After 5 years, 119 of the 304 patients given the combination developed a recurrence, compared with 177 of the 315 given no additional treatment. In addition to this significant reduction in recurrence rate, deaths were also significantly reduced.2
Levamisole is given orally 3 times a day for 3 consecutive days in each fortnight. The combined schedule with fluorouracil is followed for a year.
The combination treatment is associated with frequent adverse effects which are more common than with levamisole alone. The common adverse effects of levamisole include nausea, dysgeusia, arthralgia, fatigue and rashes. Although a flu-like illness may occur during treatment, it may be a sign of agranulocytosis. As fatalities have occurred, it is essential that the blood count is routinely monitored during therapy. Other serious adverse effects include pancreatitis and neurological changes associated with demyelination.
Patients should be warned that levamisole can produce a disulfiram-like reaction with alcohol. The drug is metabolised in the liver and may interact with anticoagulants and phenytoin.
Although most patients will have some adverse effects, the combination of levamisole and fluorouracil is likely to become the standard treatment after surgery for (Dukes' stage C) colon cancer.