PHILADELPHIA--"Six months of 5-fluorouracil (5-FU) and
leucovorin should be the new standard adjuvant therapy for patients
with node-positive, high-risk colon cancer," Daniel Haller, MD,
said at the annual ASCO meeting.
This recommendation is based on mature results of a large study
showing that 6-month adjuvant regimens of 5-FU and leucovorin are
just as effective as 12 months for preventing colon cancer
recurrence, and that levamisole adds no significant benefit.
Dr. Haller, of the University of Pennsylvania Cancer Center, reported
the final results from intergroup study INT-0089 on behalf of the
Eastern Cooperative Oncology Group, the Southwest Oncology Group, and
the Cancer and Leukemia Group B.
The study had four treatment arms: two with 6-month regimens of
5-FU/leucovorin (low dose and high dose); one with a standard
12-month regimen of 5-FU/levamisole; and one with a 6-month regimen
of all three drugs. Total accrual was 3,759 patients with high-risk
stage II or III colon cancer. Median follow-up is 5 years.
The main findings of this study (see Table)
are as follows:
There was no difference in overall survival between patients treated
with regimens combining 5-FU with either low-dose or high-dose leucovorin.
Results with the 6-month regimens were equivalent to those with the
Adding levamisole to 5-FU and low-dose leucovorin did not
significantly increase 5-year overall survival over rates with
For all patients, the only significant treatment difference was in
overall survival for those treated with 5-FU/levamisole vs 5-FU/low-dose
leucovorin/levamisole. However, the addition of levamisole to the
5-FU/low-dose leucovorin regimen conferred an insignificant 1%
improvement in overall survival.
Therefore, although the three-drug combination was statistically
superior in overall survival to standard 5-FU/levamisole, it was not
more effective than 5-FU/low-dose leucovorin alone.
There were no significant differences for any of the treatment
comparisons for the patients with high-risk stage II disease.
However, these patients comprised only 20% of the study population.
"From a statistical standpoint, levamisole happens to have been
part of the best arm of the study. From a clinical relevancy
standpoint, the absence of a relatively expensive drug with more
toxicity for little, if any, benefit would make the deletion of
levamisole perfectly appropriate," Dr. Haller said.
He pointed out that subset analysis found more side effects in the
elderly, but these side effects did not affect compliance. He noted
that the worse prognosis observed in patients over age 65 appeared to
be due to disease recurrence, not to concurrent health problems or
adverse effects of treatment.
"Patients with stage II or stage III colon cancer have a 50% to
75% chance of cure with surgery alone, but that also means that they
have a 25% to 50% risk of dying of metastatic disease within 5 years
after surgery," Dr. Haller said. "Adjuvant therapy can
improve that risk, and this trial shows that the shorter duration
regimens are at least as effective as a longer treatment program. I
think that most people will likely abandon the 12-month