A CLINICAL AND PHARMACOLOGICAL STUDY OF 5-FLUOROURACIL, LEUCOVORIN AND INTERFERON-ALFA IN ADVANCED COLORECTAL-CANCER

Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standar d treatment approach in patients with metastatic colorectal cancer. Mo dulation of FUra with interferon alfa has also shown some promise. Lab oratory data have demonstrated increased cytotoxicity when FUra is com bined with both LV and interferon. The current study examined the effe cts of double modulation of FUra using LV and interferon. Patients wit h measurable advanced colorectal cancer received bolus FUra 375 mg/m(2 ) plus LV 20 mg/m(2) daily for 5 days, repeated every 28 days. Recombi nant human interferon alfa-2a, 3 million IU/m(2) subcutaneously, was g iven daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% Cl 12.0-40.0%). Overall, 70% of p atients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P < 0.0001). Improvements in tumor-relat ed symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressi ve changes in FUra metabolism from interferon usage.