Less intense therapy yields comparable survival for some colorectal
cancer patients
Last Updated: November 03, 2004



VIENNA (Reuters Health) - The preliminary results of a new study of
advanced colorectal cancer appear to challenge the current
combination drug regimen that has become standard in the US over the
last 4 years. The new data suggest that starting patients who present
with advanced disease on 5-fluorouracil (5-FU) leads to comparable
survival compared with starting with a more toxic combination regimen.


In 1999, Dr. Leonard Saltz, of Memorial Sloan Kettering Cancer Center
in New York and Dr. Jean-Yves Douillard, of Centre René-Gauducheau,
Nantes, France, independently reported study results supporting the
addition of irinotecan to standard first-line 5-FU. Since then,
irinotecan plus 5- FU has been adopted as the new standard first-line
approach in the US.

"What they haven't proven is whether those patients may have done
equally well had the extra drugs been delivered in a sequenced way,"
said Professor Matthew Seymour, principal investigator of the Cancer
Research UK Cancer Medicine and Pathology Programme. He is based at
the University of Leeds and the Leeds Teaching Hospitals NHS Trust.

Professor Seymour said the results of the FOCUS trial provide
convincing evidence that such a sequenced approach -- starting a
patient on 5-FU alone and adding other drugs later as needed -- can
provide the same survival benefit with less toxicity when compared
with starting patients on two drugs. He presented his group's new
data this week at the 29th European Society for Medical Oncology
Congress.

In fact, he said, "giving first-line combination therapy didn't give
any better survival results than giving patients first-line 5-FU
therapy followed by a combination introduced by adding a second drug."

However, he emphasized the results do not apply to patients who are
diagnosed with disease that can be cured. For them, intensive
combination chemotherapy may be warranted from the start, even if it
exposes patients to a more toxic regimen.

The Medical Research Council's FOCUS trial, involving 2135 patients
and spanning more than 3.5 years, aimed to optimize the use of
fluorouracil, irinotecan and oxaliplatin. The subjects had
inoperable, advanced colorectal cancer that had not been treated.

The patients were randomized to one of three regimens: 5-FU alone
until treatment failure, then a switch to irinotecan alone; 5-FU
until treatment failure, then the addition of oxaliplatin or
irinotecan; or 5-FU plus irinotecan or oxaliplatin.

Professor Seymour reported that the second and third protocols
produced identical overall survival, while patients who received the
first treatment protocol did a little less well. However, the
differences were not statistically significant.

Additionally, survival and response to treatment results in the FOCUS
trial, he reported, were superior to what was reported by the last
national survey in the UK National Trial.

Median survival in the second and third protocols was 15.2 months,
with 63% of patients alive at 1 year and 23% at 2 years, versus 10
months median survival, and 40% survival at 1 year in the last UK
National Trial, CR06.

He attributes the difference to a new schedule developed by FOCUS
trial researchers called "Modified de Gramont," in which folinic acid
was administered to enhance the efficacy of 5-FU. "It performed well,
with more patients having a response, and for longer periods, than in
our previous trials, but with minimal side effects."





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