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Letrozole

Letrozole (Femara®) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer. more...

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Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letrozole blocks this activity by competitive, reversible binding to the heme of its cytochrome p450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids. In contrast, Tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, does effect its antiestrogenic action by interfering with the estrogen receptor, not the estrogen production.

Letrozole is approved by the FDA for the treatment of local or metastatic breast cancer that is hormone receptor positive or has an unknown receptor status. Side effects include signs and symptoms of hypoestrogenism. There is concern that long term use may lead to osteoporosis.

A related agent is anastrozole.

Read more at Wikipedia.org


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Study shows advantage for new breast cancer drug—many questions remain. aromatase inhibitor - letrozole Femara
From Healthfacts, 12/1/03

The news was so important that The New England Journal of Medicine announced the study results three weeks earlier than the planned publication date. The clinical trial was halted early because the new drug almost halved the risk of recurrence among women with postmenopausal estrogen-dependent breast cancer.

All of the study participants had completed the standard five-year treatment with the anti-estrogen drug called tamoxifen. Though the breast cancer recurrence rate is reduced by tamoxifen, this upsetting possibility remains long after the five-year treatment is over. The trial was designed to see whether another anti-estrogen drug, letrozole (brand name: Femara), could further reduce the risk of recurrence.

The new study, which involved over 5,000 women with early breast cancer, was sponsored by the National Cancer Institute of Canada and conducted at numerous medical centers in North America. The most encouraging finding relates to the number of women who suffered metastasized breast cancer (spread to distant organs): 47 in the letrozole group and 76 in the placebo group. As noted, the drug halved the rate of "events," which includes distant metastases, recurrences in the affected breast, and recurrences in the opposite breast. This means that the total number of recurrences or new breast cancers went from 5.1% in the placebo group to 2.9% in the letrozole group.

A closer look at this clinical trial, however, indicates that more than a few caveats are in order. The trial is said to have lasted two to four years--too short a time period to tell whether letrozole prolongs survival and not long enough to get the full picture about serious adverse reactions. Furthermore, only about one quarter of the patients were followed for 30 months or more; and less than 1% of the women received four years of treatment. Stopping the trial early means that there is no information about the optimum duration of letrozole treatment.

Letrozole belongs to a class of drugs called aromatase inhibitors (another drug in this class is anastrozole, or Arimidex). They work by blocking aromatase, the enzyme that converts androgens into estrogen, and as such stop almost all estrogen production. Earlier studies of this drug class have shown that they increase the risk of osteoporosis-related fractures, hot flashes, night sweats, musculoskeletal discomforts and sexual dysfunction.

The need for more information about aromatase inhibitors is best illustrated by the story of tamoxifen. It took many years of research to show that tamoxifen need not be given for more than five years, and that it also has a small recurrence-reduction benefit that continues for years after discontinuation. It also took years of research to learn about tamoxifen's more serious, though relatively rare, adverse effects, such as potentially fatal endometrial adenosarcoma, stroke, and blood clots.

The new findings affect a large percentage of women who will have to decide whether to take letrozole, as estrogen-receptor positive postmenopausal breast cancer is the most common form of the disease. The editorial that accompanied this study cautioned that the new findings should not be interpreted as a letrozole recommendation for all women who fit this profile.

Most of the women with the early-stage form of this type of breast cancer will survive the disease without tamoxifen or letrozole. Unfortunately, there is no test that can accurately identify the early-stage breast cancers that will not recur, and therefore do not require further treatment with tamoxifen or letrozole.

COPYRIGHT 2003 Center for Medical Consumers, Inc.
COPYRIGHT 2003 Gale Group

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