Anastrozole Beats Tamoxifen as First-Line, Adjuvant Treatment

For postmenopausal women who develop hormone-receptor-positive, localized breast cancer, the standard adjuvant hormone treatment has been 5 years of tamoxifen. But new findings from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial have confirmed that the aromatase inhibitor Arimidex (anastrozole, developed by AstraZeneca, the sponsor of this study) provides these women with prolonged disease-free survival and a longer time to recurrence, as well as fewer treatment side effects. "Five years of anastrozole should now be considered as the preferred initial adjuvant endocrine treatment," the authors wrote in the December 8 Lancet.

After a median 68 months of follow-up, the data show that women who received anastrozole had a 26 percent risk reduction over tamoxifen in time to recurrence, and a 42 percent reduced incidence of contralateral breast cancer. The researchers noted that because their patients had a relatively good prognosis at the outset, it is too early to expect a difference in survival between the treatment arms, but with the additional finding that there were fewer participant withdrawals among those receiving anastrozole - perhaps due to the fact that patients receiving it had reduced incidence of endometrial cancer, blood clots, stroke, vaginal bleeding, hot flashes, and vaginal discharge - compared with those who received tamoxifen. "It is reasonable to switch patients currently on tamoxifen to an aromatase inhibitor," the authors wrote, and "the present data suggest that it is not appropriate to wait 5 years" before making the switch.

Patients with chronic myelogenous leukemia (CML) who had developed resistance to or were intolerant of imatinib (Gleevec) responded very well to a new investigational agent, BMS-354825, researchers reported last week at the American Society of Hematology (ASH) annual meeting. In the phase I study, partially supported by NCI, 86 percent of the 36 patients with imatinib-resistant, stable CML treated with the investigational drug BMS-354825 had a complete hematologic response, meaning that their white blood cell count returned to normal, for up to 9 months, with just a few patients experiencing minor side effects. Of the 29 chronic CML patients for whom the appropriate data were available, 28 percent had a major cytogenetic response, meaning the cancer-causing cells were eliminated. Positive results were also seen for study participants in the accelerated or blast phases of CML.

Although BMS-354825 and imatinib are targeted agents, the former is less selective. Both agents bind to the BCR-ABL tyrosine kinase, a mutated form of which initiates the overproliferation of white blood cells that eventually wreaks physiologic havoc. But BMS-354825 also inhibits another kinase that may be involved in imatinib resistance, SRC, and because it is less selective, can bind to other mutated forms of BCR-ABL that are at the root of imatinib resistance. In a study published in July in Science - led by Dr. Charles Sawyers from UCLA's Jonsson Comprehensive Cancer Center, one of the co-principal investigators of the study presented at ASH - BMS-354825 was effective against 14 of the 15 imatinib-resistant CML mutations tested (see July 27 NCI Cancer Bulletin).

Both Dr. Sawyers and co-principal investigator Dr. Moshe Talpaz of M.D. Anderson Cancer Center cautioned that these were preliminary results and that larger studies are needed to confirm the safety and effectiveness of this new agent. The drug's manufacturer, Bristol-Myers Squibb, announced during the ASH meeting that the company is moving rapidly to get the agent into phase II trials.

A Broken Promise to Our Children: The 1998 State Tobacco Settlement Six Years Later, finds that nearly every state is failing to provide adequate funding for tobacco control programs. The report, prepared by the Campaign for Tobacco-Free Kids, finds that in the current budget year only four states - Maine, Delaware, Mississippi, and Arkansas - are funding their tobacco prevention programs at or close to the levels recommended by the Centers for Disease Control and Prevention (CDC). While an additional 10 states fund tobacco prevention programs at about half the minimum the CDC recommends, the remaining 36 states and the District of Columbia provide less than half the CDC minimum, or provide no state funding whatsoever. All told, states spend $1 on tobacco prevention for every $23 spent by the tobacco industry to market tobacco products, despite receiving record levels of tobacco-generated revenue from the tobacco settlement and tobacco taxes. The Campaign for Tobacco-Free Kids is a coalition of more than 130 organizations committed to reducing tobacco use among both children and adults. Reflecting on the new report, Dr. John Seffrin, CEO of the American Cancer Society, stated, "This report shows a missed opportunity for states to save money and, more importantly, lives." The report can be viewed at http://www.tobaccofreekids.org/reports/settlements/.

Variations in state tobacco control funding and use of evidence-based interventions affect smoking prevalence and ultimately, smoking-caused disease. See the November 23 Director's Update in the NCI Cancer Bulletin for more information on a study of state-specific prevalence of cigarette smoking among adults.