Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity. Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs. 