Levamisole/fluorouracil. A review of their pharmacology and adjuvant therapeutic use in colorectal cancer.

The combination of the antimetabolite fluorouracil plus the immunomodulator levamisole is used as adjuvant therapy following surgical tumour removal in patients with Dukes' stage C colon cancer. Fluorouracil given alone in this setting results in only a modest improvement in survival rate, and levamisole monotherapy is clinically ineffective. Well controlled studies, however, demonstrate that combined levamisole/fluorouracil reduces the recurrence rate by between 31 and 41% and the total mortality rate by between 13 and 33% compared with surgery alone in patients with Dukes' stage C colon cancer after median follow-up of 3 or 7.75 years. The median time to recurrence and median survival time are also extended significantly by levamisole/fluorouracil compared with fluorouracil alone or no adjuvant treatment. Thus, levamisole/fluorouracil has been recommended as the standard adjuvant therapy for patients with Dukes' C colon cancer, against which new investigative regimens should be compared. Methods for optimising the impressive results already achieved with this combination, and using this as a basis for further progress should be the thrust of future trials.