Results of a phase III multicenter European study reported in a recent issue of the European Journal of Cancer demonstrate that anastrozole(Drug information on anastrozole) (Arimidex), a new aromatase inhibitor, in doses of 1 and 10 mg orally once daily, is an effective treatment for advanced breast cancer in postmenopausal women whose disease has progressed following therapy with tamoxifen(Drug information on tamoxifen) (Nolvadex). Results of this study combined with a US study were the basis for the December 27, 1995, FDA clearance for 1-mg anastrozole tablets.
The phase III trial investigated the efficacy and tolerability of two blinded doses of anastrozole compared to megestrol(Drug information on megestrol) acetate at its recommended therapeutic dose (40 mg four times daily) in the treatment of postmenopausal women with advanced breast cancer. Of the 378 patients enrolled in the study, 135 were randomized to 1 mg of anastrozole, 118 to 10 mg of the new drug, and 125 to megestrol.
Clinical Benefit
After a median follow-up of 6.1 months, there were no statistically significant differences between either dose of anastrozole and megestrol acetate in terms of objective tumor response rate and time to objective disease progression.
Approximately one-third of the patients had either an objective response (complete or partial response) or stabilization of their disease for more than 24 weeks. The sites of metastatic disease were similar across treatment groups; approximately 40% of the patients had soft-tissue metastases, 60% had bone metastases, and 40% had visceral (20% liver) metastases. Some patients had more than one disease site. Of patients who had a complete or partial response to anastrozole, 74% continued to respond for more than 24 weeks.
Low Incidence of Weight Gain With Anastrozole
Of the women in the study who were treated with megestrol, 8% experienced drug-related weight gain of at least 5% to 10%, which was significantly greater than the incidence of this side effect in those treated with either dose of anastrozole (2.2% for the 1-mg dose and 3.4% for the 10-mg dose). In addition, 4.8% of the women treated with megestrol experienced thromboembolic disease, compared with 0.9% of the patients on 10 mg of anastrozole and 3.7% of those on 1 mg.
"The results of this study confirm the efficacy of Arimidex in treating patients with advanced breast cancer. In addition, the trial indicates that Arimidex provides well-tolerated therapy," says Paul Plourde, MD, Senior Director of Clinical Research, Zeneca Pharmaceuticals.
Tolerability
The most frequently reported side effects considered to be drug-related by the investigators were weight gain (8%) and dyspnea (5.6%) in patients treated with megestrol acetate. In addition to weight gain reported as a side effect among patients given megestrol, an actual weight gain of at least 5% was recorded in 35% of these patients and a 10% gain was recorded in 12%.
"Prospectively planned analyses demonstrated that patients on megestrol acetate had significant weight gain," reports Dr. Plourde. "In addition, this weight gain continued in patients who remained on megestrol acetate for longer periods of time."
Most commonly reported side effects of anastrozole in combined studies (this study and a US study), included headache, hot flushes, nausea, asthenia, pain, and back pain.
In the US, anastrozole is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. Patients with estrogen-receptor-negative disease and patients who do not respond to tamoxifen rarely respond to anastrozole.
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