Combining 5-fluorouracil with interferon-alpha in the treatment of advanced colorectal cancer: optimism followed by disappointment.
Pre-clinical data have demonstrated synergy between 5-fluorouracil (5-FU) and interferon (IFN)-alpha in colon cancer cell lines. In 1989 the first small single-institution phase II study with this combination in advanced colorectal cancer showed a response of 81% with substantial toxicity, whereas IFN-alpha alone was virtually inactive. Ten published phase II studies including 175 evaluable patients have demonstrated a response rate of 2.3%. 5-FU alone has been used extensively and is moderately active with response rates of 10-11% in 1148 patients evaluated by the Advanced Colorectal Cancer Meta-analysis Project in 1992 and 1994. Eleven subsequent phase II studies with 5-FU + IFN-alpha published over the period of 1990-1994 on 548 patients showed a response rate of 28% with 2% toxic deaths. Recently, nine phase III clinical trials including 1727 randomized patients have compared 5-FU + IFN-alpha to some standard therapies, most often treatment regimens based on 5-FU + leucovorin. Except for one study involving 105 patients, the rest of the phase III studies have demonstrated either no difference (six studies) or significantly worse results (two studies showing substantial toxicity with IFN-alpha + 5-FU). Several studies are ongoing, but results are not likely to change. In conclusion, after a period of high hopes, the combination of 5-FU + IFN-alpha does not seem to fulfill the original expectations. It is costly, it is toxic and it is not effective. New treatment strategies must be developed if progress is to be obtained.
Kjaer
M
M
Department of Oncology, Aalborg Hospital Section South, Denmark.
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D005472:Fluorouracil