Director's Update: October 14, 2003
Last week, the cancer community received encouraging news about letrozole, a new breast cancer agent that, when used in a clinical trial as a follow-on to tamoxifen therapy, substantially cut the rate of tumor recurrence. This finding offers breast cancer survivors new hope for long-term and disease-free survival. And, as a new agent for controlling cancer, letrozole is further evidence of the fact that we are moving into an era in which we can successfully preempt the cancer process by preventing, eliminating, or modulating the disease.
Tamoxifen already is a valuable weapon in our preemption arsenal. It is routinely given to women successfully treated for a primary, estrogen-sensitive breast cancer to lessen their chance for tumor recurrence. (It also effectively prevents primary breast tumors in women who are at heightened risk for the disease.) Clinical trials have shown, however, that tamoxifen should only be taken for the first five years after diagnosis. Unfortunately, women continue to have recurrent tumors beyond this five-year period. This is a considerable concern, given that approximately one million women worldwide are currently taking adjuvant tamoxifen and hundreds of thousands of women complete the five-year therapy regimen every year. The letrozole study suggests that this new agent, taken after tamoxifen therapy is completed, can serve as a "next step" in our efforts to reduce the risk for recurrence in breast cancer survivors.
Begun just five years ago, the international clinical trial on letrozole enrolled more than 5,000 post-menopausal patients who had completed five years of tamoxifen therapy. Participants were randomized to two arms, one receiving letrozole (a hormonal therapy that suppresses estrogen) and one a placebo. The trial was halted early - and patients on placebo were given the option to switch to letrozole - when trial data showed that the drug reduced the risk of recurrence by 43 percent and early trends in the data showed that deaths due to breast cancer were almost halved. The fact that this large trial opened in 1998 and we have results available already is a testament to the importance of good study design and collaboration. The success of this trial is also a testament to the value of public-private partnerships, as it was coordinated and funded jointly by the NCI, the Canadian Cancer Society, and Novartis Pharmaceuticals.
While the cancer community can be encouraged by the findings of this clinical trial, many questions about letrozole still remain for future studies. For example, What are the effects of long-term use? and What is the optimal duration of treatment? While the ultimate magnitude of the survival benefit to be gained from letrozole requires further follow-up, the significant reduction in recurrent disease will have a major and immediate public health impact. For this reason, it was appropriate for the trial's Data and Safety Monitoring Committee to halt the study early. But we must recognize the need for ongoing surveillance of possible long-term side effects. This area of early approval followed by careful post-marketing surveillance presents a potential initiative for the NCI/FDA Oncology Task Force.
The results of this trial - and others like it - bring us appreciably closer to the day when people can live with, and not die from, cancer.
Andrew C. von Eschenbach, M.D.
Director, National Cancer Institute
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