42nd Annual Meeting

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Exemestane Following Tamoxifen Extends Survival in Women with Breast Cancer

Speaker: Judith Bliss, MD, Professor of Medicine, and Director, Institute for Cancer Research, Clinical Trials and Statistics Unit, London, England

(Dr. Bliss spoke for the principal investigator, Raaul C. Coombes, MD, PhD, Professor of Medical Oncology, and Head, Department of Oncology, Imperial College of London, London, England.)

A long-term analysis from a large-scale international clinical trial indicates that postmenopausal women with early breast cancer who were switched to exemestane (Aromasin, Pfizer) after two or three years of tamoxifen therapy (Nolvadex generic, Astra Zeneca) experienced a significant improvement in survival and a marked reduction in the risk of breast cancer recurrence and metastasis compared with women who continued taking tamoxifen.

These findings were concluded from the first mature analysis of the Intergroup Exemestane Study, a randomized trial begun in 1998. The study enrolled 4,724 women from 37 countries. All of these patients had been treated for early breast cancer and had been disease-free after two to three years of tamoxifen treatment. Upon entry into the trial, the women were selected to switch to exemestane for an additional two or three years to complete five years of treatment or to continue with tamoxifen for a total of five years of treatment.

At a median follow-up of 4.8 years, an analysis was carried out in two groups of patients. An intent-to-treat (ITT) group included 122 patients with unknown estrogen receptor (ER) status; these patients were later found to be ER-negative, and the analysis was repeated to exclude the ER-negative patients.

Overall, in the ITT population, there were 808 first events: 354 in the exemestane group and 454 in the tamoxifen group. Those using exemestane had a 24% lower risk of experiencing any first event, a 44% lower incidence of cancer in the contralateral breast, and a 17% reduction in the risk of metastasis, thus resulting in improved disease-free survival. In addition, women receiving exemestane had a 15% lower risk of dying of any cause than the women who continued using tamoxifen, thereby leading to improved overall survival.

Although there were no significant differences between the two treatment groups in terms of myocardial infarction, angina, or stroke, those continuing tamoxifen treatment tended to have more thromboembolic events (blood clots) and serious gynecologic events (uterine cancer, polyps, and vaginal bleeding). By contrast, patients receiving exemestane had a slightly higher number of bone fractures, a consequence that points to the need for bone density monitoring during exemestane therapy.

Modafinil Improves Quality of Life in Patients with Brain Tumors

Speaker: Thomas A. Kaleita, PhD, Assistant Clinical Professor, Department of Psychiatry, David Geffen School of Medicine at University of California, Los Angeles, and Neuro-oncology Program, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California

Modafinil (Provigil, Cephalon), a drug used for a variety of sleep disorders, has been shown to enhance the quality of life in patients with malignant and nonmalignant cerebral tumors, improving cognitive function, mood, and fatigue levels with a low incidence of adverse drug effects (ADEs).

Thirty patients, 21 to 65 years of age, were treated with neurosurgical resection, radiation, and/or chemotherapy. They were randomly assigned to receive modafinil 200 mg or 400 mg daily in divided doses for three weeks. This regimen was followed by a one-week washout period in which patients did not receive any drug at all. All of the patients were then entered into an eight-week, open-label extension phase during which they were given modafinil at doses determined to be optimal for each individual. The doses varied between 50 and 600 mg/day.

The researchers performed evaluations based on changes from baseline during scheduled visits at one, three, four, eight, and 12 weeks. Standardized tests were used to measure concentration, attention, fatigue, and mood evaluation and to identify specific symptoms of depression. These instruments included Parts A and B of the Trail Making Test, the Symbol Digit Modalities Test, the Verbal Fluency Test, the Hamilton Depression Scale, the Fatigue Severity Scale, the Visual Analogue Fatigue Scale, and the Modified Fatigue Impact Scale. Patients also received comprehensive neurological examinations at specific times and underwent brain magnetic resonance imaging before, during, and after the study.
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In a comparison of various test scores at baseline and after eight weeks and 12 weeks of treatment, most patients showed statistically significant, as well as clinically meaningful, improvement in all tests. Test scores in cognitive abilities improved by an average of 21%; mood, by 35%; and fatigue, by 47%. The greatest improvements were observed at eight weeks.

Three patients did not respond to modafinil, possibly because of the tumor site or psychological factors.