[Biomodulation of 5-fluorouracil by interferon].

The biomodulation (BM) of 5-fluorouracil (5-FU) by interferon (IFN) is reviewed both preclinically and clinically, stressing clinical relevance. A number of preclinical evaluations of a combination of 5-FU and IFN were performed before Wadler et al. developed an active biomodulation therapy with a combination of 5-FU and IFN. However, extensive preclinical investigations have been performed very recently showing that IFN can enhance cytotoxic effects of 5-FU through various mechanisms, not only by increased anabolism of 5-FU to 5-fluoro 2'-deoxyuridine monophosphate (FdUMP) or 5-fluorouridine (FUR), inhibition of thymidine kinase activity, possible alternation of pharmacokinetics of 5-FU, but also by biological response modification. Since a high response rate of 76.4% in patients with previously untreated advanced metastatic colorectal cancer was reported by Wadler et al., with the combination of 5-FU and IFN, consecutive extensive phase II studies of the combination have been undertaken and shown a modest response rate ranging from 25% to 43% for colorectal cancer. An attempt to add leucovorin (LV) to the combination of 5-FU and IFN has so far appeared less successful. It showed almost the same efficacy in terms of response rate and survival, but more significant side effects. A further study is warranted to evaluate the optimal dose and schedule of IFN in combination with 5-FU or the 5-FU and LV combination chemotherapy in the proper sense of biomodulation. The role of biomodulating chemotherapy of 5-FU by IFN or IFN and LV must also be investigated in the field of head and neck cancers, esophageal cancer, biliary tract cancer, all of which are relatively sensitive to the effector of 5-FU.