Comparison of fluorouracil with additional levamisole, higher-dose folinicacid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial
Rg. Gray et al., Comparison of fluorouracil with additional levamisole, higher-dose folinicacid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial, LANCET, 355(9215), 2000, pp. 1588-1596
Citations number
13
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background Standard adjuvant chemotherapy for colorectal cancer consists of
fluorouracil with folinic acid or levamisole. The large QUASAR randomised
trial aimed to investigate (in a two x two design) whether use of a higher
dose of folinic acid or addition of levamisole to fluorouracil and folinic
acid improved survival.
Methods Patients with colorectal cancer, without evident residual disease,
were randomly assigned fluorouracil (370 mg/m(2)) with high-dose (175 mg) o
r low-dose (15 mg) L-folinic acid and either active or placebo levamisole.
The fluorouracil and folinic acid could be given either as six 5-day course
s with 4 weeks between the start of the courses or as 30 once-weekly doses.
Levamisole (50 mg) or placebo was given three times daily for 3 days repea
ted every 2 weeks for 12 courses. The primary endpoint was mortality from a
ny cause. Analyses were by intention to treat.
Findings Between 1994 and 1997, 4927 patients were enrolled. 1776 had recur
rences and 1576 died. Survival was similar with high-dose and low-dose foli
nic acid (70.1% vs 71.0% at 3 years; p=0.43), as were 3-year recurrence rat
es (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with p
lacebo (69.4% vs 71.5% at 3 years; p=0.06). and there were more recurrences
with the active drug (37.0% vs 34.9% at 3 years; p=0.16).
Interpretation The inclusion of levamisole in chemotherapy regimens for col
orectal cancer does not delay recurrence or improve survival. Higher-dose f
olinic acid produced no extra benefit in these regimens over that from low-
dose folinic acid. Trials of chemotherapy versus no chemotherapy will show
whether these four treatments are equally effective or equally ineffective.