Early adjuvant trials were retrospective and underpowered
and
failed to show any therapeutic benefit with respect to
recurrence
rate or survival. In 1990, however, the results of the
intergroup
trial were published. In this study 318 patients with
stage B
colorectal malignancy were randomised for surgical treatment
alone or surgery followed by fluorouracil plus levamisole.
In
addition, 929 patients with stage C malignancy received
surgery
alone, surgery plus levamisole, or surgery plus fluorouracil
and
levamisole. For these patients there was a 33% reduction
in the
odds of death and a 41% decrease in recurrence among
those
treated with fluorouracil plus levamisole compared with
surgery
alone or surgery plus levamisole.
In contrast with levamisole, combining folinic acid with
fluorouracil is pharmacologically rational, and documented
benefit in advanced disease led to the logical extension
of this
combination into adjuvant therapy. Three large randomised
adjuvant phase III trials produced confirmatory evidence
of
improved, disease-free survival at three years and improved
overall survival in patients treated with fluorouracil
plus folinic
acid, with a 25-30% decrease in the odds of dying from
colon
cancer (or an absolute improvement in survival of 5-6%
compared with controls).
Recently a meta-analysis of updated individual data from
all
unconfounded randomised studies of adjuvant chemotherapy
(including the above three trials) has been undertaken
(Colorectal Cancer Collaborative Group, unpublished).
Overall,
there was a 6-7% absolute improvement in survival with
chemotherapy compared with surgery alone (SD 2.3, P =
0.01).
The analysis advised that on current evidence the combination
of fluorouracil plus folinic acid should be accepted
as
“standard” adjuvant chemotherapy for patients with Dukes’s
type C colon cancer. |
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