SAN ANTONIO--The NCI's clinical alert advising physicians to limit
the use of tamoxifen (Nolva-dex) in early breast cancer to no
more than 5 years may be a "premature judgment" that
was based on a randomized trial of insufficient size, Prof. Richard
Peto, of the University of Oxford's ICRF Clinical Trial Service
Unit, said at the San Antonio Breast Cancer Symposium.
How long should tamoxifen treatment continue? "Current trials
are too small to provide a reliable answer," Prof. Peto said.
Worldwide, he continued, the numbers of women who have been randomized
between different durations of tamoxifen are not yet adequate.
The trials of 1 year vs longer treatment involved only about 2,000
women; trials comparing 2 years with 5 years of tamoxifen are
in progress but have not yet produced mature data; and trials
of 5 years vs longer treatment involve fewer than 2,000 women,
and these trials have now been stopped, Prof. Peto said.
"The year 2000 overview will bring together the data from
all of these trials, and then we will have really good evidence
on 5 years vs 2 years of treatment," he said. But even then
the question of whether continuing treatment for more than 5 years
produces additional benefits may be difficult to answer reliably.
"The main trial [NSABP B-14] of 5 years vs 10 years, with
more than 1,000 randomized women, has just been shut down due
to what may, in retrospect, turn out to be a misleading alarm
by the data monitoring committee," Prof. Peto said. "So,
at the moment, we have no directly randomized evidence on 5 years
vs longer in the pipeline, unless new studies can be started and
made to work."
One such trial being planned is the Adjuvant Tamoxifen Longer
Against Shorter (ATLAS) study, funded by the US Army, which aims
to randomize 20,000 women. "That's the appropriate scale,"
Prof. Peto said. "We'll find out whether it is possible or
not to perform such a study over the next few years."
In his talk, Prof. Peto reported the preliminary results of the
recent Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
metaanalysis of tamoxifen trials, which is currently being prepared
for publication. [An updated metaanalysis of the effects of radiotherapy
and surgery in early breast cancer appeared last November (N Engl
J Med 333:1444-1455, 1995)].