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ASCO releases new guidelines on breast cancer.
For years, tamoxifen (Nolvadex, AstraZeneca) has been the standard adjuvant treatment for certain types of breast cancer. It has also been used as a preventive agent in women at high risk for developing breast cancer. "Tamoxifen is the gold standard," said Brenna Brown, Pharm.D., BCOP, clinical oncology pharmacist at the H. Lee Moffitt Cancer Center in Tampa, Fla.
Another treatment that may now prove as effective as tamoxifen at preventing cancer recurrence is anastrozole (Arimidex, AstraZeneca), an aromatase inhibitor. It was the subject of an American Society of Clinical Oncology (ASCO) status report published recently in the Journal of Clinical Oncology and on the journal's Web site.
ASCO reviewed the results of several trials and outlined its recommendations. It focused primarily on the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial. This trial, which began in July of 1996 and ended in March 2000, included more than 9,000 postmenopausal women with hormone receptor-positive (or unknown) breast cancer. Preliminary results from the ATAC trial indicate that anastrozole is at least as effective as tamoxifen, and possibly more so. Fewer women suffered cancer recurrence when treated with anastrozolea statistically significant number, according to the researchers.
While ASCO concluded that the ATAC evidence was sufficient to recommend anastrozole as an alternative to tamoxifen, it did not see proof that the agent actually outperforms tamoxifen. "The absolute difference in the percentage of patients who were disease-free at follow-up is 2.02% (89.86% v 87.84%)."
Applied to the entire population of breast cancer patients, is the 2% advantage significant? "Yes, it is," said Regina Holdstock, R.Ph., BCOP, senior attending pharmacist at Massachusetts General Hospital Cancer Center in Boston. About 70% to 80% of breast cancer tumors are hormone receptor-positive, and 2% of the thousands of women battling breast cancer could be substantial.
Tamoxifen and the aromatase inhibitors (AIs) battle estrogen in different ways. Tamoxifen competes with estrogen for estrogen receptors. Tumors requiring estrogen for growth are thus deprived of the hormone.
The AIs use a different tactic. "The aromatase inhibitors block conversion of androgens to estrone and estradiol in peripheral tissues," Holdstock explained. "So, basically, the result is decreased circulation estrogen." This decrease of estrogen may result in cellular apoptosis in the tumor.
Since tamoxifen has been on the market, a number of serious adverse effects have been documented. Endometrial cancer and thromboembolic events occur more commonly in women taking tamoxifen than placebo or anastrozole. Other side effects include vaginal bleeding, menstrual irregularities, and hypercalcemia, according to the labeling; the most common are hot flashes.
The types of adverse effects reported during ATAC were quite similar to those of tamoxifen. Anastrozole did not produce nearly as many serious adverse effects as tamoxifen during the ATAC trial. It was, however, associated with a much higher incidence of fractures and musculoskeletal disorders. "The thought of skeletal effects in this population is quite alarming," said Holdstock. These patients are already at risk for osteoporosis because of their age and diagnosis.
It should be mentioned that anastrozole is indicated only for postmenopausal patients. The AIs have not worked well in premenopausal women because their hormonal systems offset the drugs' estrogen-lowering effects. "There's absolutely no indication that [AIs] would be of benefit in premenopausal women," said Holdstock, referring to AI use as monotherapy in women with functioning ovaries. Tamoxifen does not have this limitation; it can be used in both pre- and postmenopausal women.
After weighing all the evidence, ASCO concluded that while anastrozole does appear to be a promising agent, tamoxifen is still the standard adjuvant therapy for women with hormone receptor-positive breast cancer. The evidence does support anastrozole as a safe and efficacious alternative to tamoxifen. This is quite similar to the conclusion reached by the National Comprehensive Cancer Network (NCCN) in 2002 (see Drug Topics, April 1, 2002).
Both Brown and Holdstock agreed with ASCO and NCCN. Another big consideration, Brown added, is that tamoxifen is available generically and is therefore much less expensive than anastrozole. Many patients with breast cancer are elderly and paying for their own medication, so this is extremely important for them.
That said, Brown pointed out that the efficacy of the aromatase inhibitors is quite good. "The main drawback with them right now is that they have not been on the market very long," she said. "I think that in the future they may come to surpass tamoxifen."
"I do believe the AIs may prove to be as good as or better [than tamoxifen]," said Holdstock. For now, though, she added, "if I had breast cancer, I would be starting myself on tamoxifen."
Jillene Lewis. Breast cancer guidelines suggest alternative to standard therapy.
Aug. 18, 2003;147:22.