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Oncology NEWS International. Vol. 5 No. 1
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Limits on Tamoxifen Duration Questioned

January 1, 1996

SAN ANTONIO--The NCI's clinical alert advising physicians to limit the use of tamoxifen(Drug information on 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)].

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