Fluorouracil and leucovorin with or without interferon alfa-2a as
adjuvant treatment, 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. Pharmacological studies of FU led to its use in
combination with a number of modulating agents including interferon-a
and leucovorin (LV) that appear to enhance its activity in vitro.
Furthermore, a meta-analysis suggested that the combination of FU with
LV increased the response rate as compared to FU monotherapy in patients
with advanced colorectal cancer. Purpose: To evaluate the impact of
adjuvant treatment with the combination of FU and LV with or without
interferon alfa-2a (IFN) on disease-free survival (DFS) and overall
survival (OS) for patients with stage II or III colon cancer. Patients
and Methods: From August 1989 to July 1997, 280 patients with stage II
and III colon 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 recombinant IFN (3 MU subcutaneously 3 times a
week) for 1 year (group B, 141 patients). 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 of 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 was not
included in the analysis. The median relative dose intensity of FU in
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
either 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 of infiltrated nodes, tumor grade and presence of
regional implants were identified as significant prognostic factors for
OS. Grade 3-4 toxicities, mainly 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 DFS and OS of
patients with stage II or III colon cancer. Copyright (C) 2000 S. Karger
AG, Basel
