Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvanttreatment, in patients with high-risk colon cancer - A randomized phase III study conducted by the Hellenic Cooperative Oncology Group

Background: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacol ogical studies of FU led to its use in combination with a number of modulat ing agents including interferon-a and leucovorin (LV) that appear to enhanc e its activity in vitro. Furthermore, a meta-analysis suggested that the co mbination of FU with LV increased the response rate as compared to FU monot herapy in patients with advanced colorectal cancer. Purpose: To evaluate th e impact of adjuvant treatment with the combination of FU and LV with or wi thout interferon alfa-2a (IFN) on disease-free survival (DFS) and overall s urvival (OS) for patients with stage II or III colon cancer. Patients and M ethods: From August 1989 to July 1997, 280 patients with stage II and III c olon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m(2)/week x 6, followed by a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombi nant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 pati ents). Results: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B complated four cycles of chemotherapy. Also, 51.4% of patients o f group A and 53.9% of group B received greater than or equal to 80% of the planned dose of FU. One patient (group A) was found to be ineligible and w as not included in the analysis. The median relative dose intensity of FU i n the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in eithe r 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84. 5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number o f infiltrated nodes, tumor grade and presence of regional implants were ide ntified as significant prognostic factors for OS. Grade 3-4 toxicities, mai nly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B, There were no treatment-related deaths. Conclusions: The addition of IFN to the combination of FU with LV postoperatively does not improve D FS and OS of patients with stage II or III colon cancer. Copyright (C) 2000 S. Karger AG, Basel.