MONTREAL, Canada--Tomudex (ZD1694), a new direct and specific
thymidylate synthase (TS) inhibitor, has been shown to be especially
promising for the treatment of patients with advanced colorectal
cancer, David Cunningham, MD, said at the 19th International Congress
The new TS inhibitor has antitumor activity at least as effective
as the best standard therapy with the prototypic TS inhibitor
fluorouracil in combination with leucovorin, while having significantly
fewer life-threatening side effects and producing better palliative
results, said Dr. Cunningham, consultant oncologist, Institute
for Cancer Research and the Royal Marsden Hospital, Sutton, UK.
These conclusions were reached from a comparative phase III clinical
trial in which 439 patients with previously untreated colorectal
cancer were randomized to Tomudex, 3.0 mg/m² IV as a single
dose once every 3 weeks (222 patients), or fluorouracil, 425 mg/m²,
and leuco-vorin, 20 mg/m², as an IV bolus daily for 5 days
every 4 or 5 weeks.
Five randomized patients did not receive therapy, but all individuals
who received trial treatments, whether or not they were eligible
or evaluable, were included in the analysis.
With a median follow-up of 5.3 months, the overall response rate
was 20% in the Tomudex-treated patients (2% complete response
and 18% partial response) vs 13% for patients receiving fluorouracil
and leucovorin (2% complete response and 11% partial response),
Dr. Cunningham noted.
In addition, 21 patients in the Tomu-dex group and six on fluorouracil
and leucovorin had 40% to 50% reductions in measurable lesion
size, strongly suggesting that with a longer follow-up, the results
would be even more favorable with regard to Tomudex treatment,