Sequential Biochemical Modulation of Fluorouracil With Folinic Acid, N-Phosphonacetyl-L-Aspartic Acid, and Interferon Alfa-2a in Advanced Colorectal Cancer

Abstract

PURPOSE: Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNα-2a) in a sequential order to assess the efficacy of this approach in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Forty-four patients with metastatic colorectal carcinoma were enrolled onto the study. The treatment course consisted of three cycles: (cycle 1) FA 20 mg/m2 followed by 5-FU 425 mg/m2 on days 1 to 5; (cycle 2) PALA 250 mg/m2 on days 29, 36, 43, and 50 and 5-FU 2,600 mg/m2 as a 24-hour infusion on days 30, 37, 44, and 51; and (cycle 3) IFNα-2a 9 million units (MU) three times a week for 5 weeks beginning on day 57, with a continuous infusion of 5-FU 750 mg/m2 on days 57 to 61, and then weekly bolus of 5-FU 750mg/m2/wk on days 71, 78, and 85. Response was determined after cycle 3. RESULTS: All patients had a Zubrod performance status ≥ 2, measurable disease, and had received no prior chemotherapy for their metastatic disease. A total of 212 cycles were given. Thirty-six patients were assessable for response. No complete responses were seen. Seven patients had a partial response, eight had stable disease, and 15 had progressive disease. The median duration of response was 25 weeks, and the median survival was 53 weeks. Grade 3 and 4 toxic effects included granulocytopenia, stomatitis, diarrhea, rash, nausea, and fatigue. CONCLUSION: This trial provided no evidence that sequential biochemical modulation of 5-FU in patients with metastatic colorectal carcinoma had any therapeutic advantage over conventional treatment regimens of 5-FU plus FA.