47 research outputs found
Breast cancer research and the European Union Clinical Trials Directive
Running clinical trials in the commercial sector has always been associated with a certain amount of bureaucracy due to the stringent requirements needed to bring a new drug onto the market. Noncommercial trials have largely been performed outside these requirements. New legislation brought about as a result of the implementation of the European Union Clinical Trials Directive will change this two-tiered approach by harmonizing regulations in all member states. Those who run noncommercial clinical trials will have to find cost-effective ways of dealing with this legislation if such work is to continue in Europe
Anastrozole-related acute hepatitis with autoimmune features: a case report
<p>Abstract</p> <p>Background</p> <p>Two cases of acute hepatitis occurring during treatment with anastrozole have previously been reported, but the underlying mechanisms of liver injury are still uncertain. We report the case of anastrozole-related acute hepatitis with some autoimmune features.</p> <p>Case presentation</p> <p>A 70-year-old woman developed acute hepatitis associated with serum antinuclear antibodies during anastrozole treatment; after drug withdrawal, liver function parameters rapidly improved and serum auto-antibodies were no longer detectable.</p> <p>Conclusions</p> <p>Anastrozole-induced hepatotoxicity is a very rare event. Drug-drug interactions or metabolically-mediated damage might be involved, with a possible role of individual susceptibility. Our report suggests that an immune-mediated mechanism may also be considered in anastrozole-related liver injury.</p
Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)—a randomised controlled trial of exemestane versus continued tamoxifen after 2–3 years tamoxifen
Background: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen
Safety of aromatase inhibitors in the adjuvant setting
The third-generation aromatase inhibitors (AIs) letrozole, anastrozole, and exemestane are replacing tamoxifen as adjuvant therapy in most postmenopausal women with early breast cancer. Although AIs have demonstrated superior efficacy and better overall safety compared with tamoxifen in randomized controlled trials, they may not provide the cardioprotective effects of tamoxifen, and bone loss may be a concern with their long-term adjuvant use. Patients require regular bone mineral density monitoring, and prophylactic bisphosphonates are being evaluated to determine whether they may protect long-term bone health. AIs decrease the risks of thromboembolic and cerebrovascular events compared with tamoxifen, and the overall rate of cardiovascular events in patients treated with AIs is within the range seen in age-matched, non-breast-cancer populations. AIs are also associated with a lower incidence of endometrial cancer and fewer vaginal bleeding/discharge events than tamoxifen. Compared with tamoxifen, the incidence of hot flashes is lower with anastrozole and letrozole but may be higher with exemestane. Generally, adverse events with AIs are predictable and manageable, whereas tamoxifen may be associated with life-threatening events in a minority of patients. Overall, the benefits of AIs over tamoxifen are achieved without compromising overall quality of life
Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses
Copyright © 2003 American Cancer Societ
Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial
Background: Little data exist on whether efficacy benefits or side-effects persist after 5 years of adjuvant treatment with an aromatase inhibitor. We aimed to study long-term outcomes in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial that compares anastrozole with tamoxifen after a median follow-up of 100 months. Methods: We analysed postmenopausal women with localised invasive breast cancer. The primary endpoint disease-free survival (DFS), and the secondary endpoints time to recurrence (TTR), incidence of new contralateral breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS), and death after recurrence were assessed in the total population (intention to treat; ITT: anastrozole, n=3125; tamoxifen, n=3116; total 6241) and the hormone-receptor-positive subpopulation, the clinically important subgroup for which endocrine treatment is now known to be effective (84% of ITT: anastrozole, n=2618; tamoxifen, n=2598; total 5216). After treatment completion, fractures and serious adverse events continued to be collected blindly (safety population: anastrozole, n=3092; tamoxifen, n=3094; total 6186). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. Findings: At a median follow-up of 100 months (range 0–126), DFS, TTR, TTDR, and CLBC were improved significantly in the ITT and hormone-receptor-positive populations. For hormone-receptor-positive patients: DFS hazard ratio (HR) 0·85 (95% CI 0·76–0·94), p=0·003; TTR HR 0·76 (0·67–0·87), p=0·0001; TTDR HR 0·84 (0·72–0·97), p=0·022; and CLBC HR 0·60 (0·42–0·85), p=0·004. Absolute differences in time to recurrence increased over time (TTR 2·8% [anastrozole 9·7% vs tamoxifen 12·5%] at 5 years and 4·8% [anastrozole 17·0% vs tamoxifen 21·8%] at 9 years) and recurrence rates remained significantly lower on anastrozole compared with tamoxifen after treatment completion (HR 0·75 [0·61–0·94], p=0·01). The fewer deaths after recurrence (anastrozole 245 vs tamoxifen 269) was not significant (HR 0·90 [0·75–1·07], p=0·2), and no effect was noted for OS (anastrozole 472 vs tamoxifen 477) HR 0·97 [0·86–1·11], p=0·7). Fracture rates were higher in patients receiving anastrozole than in those receiving tamoxifen during active treatment (number [annual rate]: 375 [2·93%] vs 234 [1·90%]; incidence rate ratio [IRR] 1·55 [1·31–1·83], p<0·0001), but were not different after treatment was completed (off treatment: 146 [1·56%] vs 143 [1·51%]; IRR 1·03 [0·81–1·31], p=0·79). We did not note any significant difference in risk of cardiovascular morbidity or mortality between anastrozole and tamoxifen treatment groups. Interpretation: These data show long-term safety findings and establish clearly the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant treatment for postmenopausal women with hormone-sensitive, early breast cancer, and provide statistically significant evidence of a larger carryover effect after 5 years of adjuvant treatment with anastrozole compared with tamoxifen
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A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma
BACKGROUND
Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily, and megestrol acetate, given in doses of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy.
METHODS
The trial was randomized, double blind for anastrozole, open label for megestrol acetate, parallel group, and multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n = 128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary efficacy measures were time to progression and tumor response; secondary measures were time to treatment failure, duration of response, quality of life, and time to death.
RESULTS
With a median duration of follow‐up of 6 months, there was no statistical evidence of a difference between either 1 or 10 mg doses of anastrozole and megestrol acetate for any efficacy endpoint. According to rigid response criteria, 10%, 6%, and 6% of patients in the anastrozole 1 mg, anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective response (complete response or partial response) and 27%, 24%, and 30% of patients in the respective groups had stable disease for a duration of 24 weeks or longer. Quality‐of‐life assessments revealed that anastrozole in a 1‐mg dose was associated with better physical scores and anastrozole in a 10‐mg dose with better psychologic scores than megestrol acetate. Both anastrozole and megestrol acetate were generally well tolerated. Among anticipated adverse events, gastrointestinal disturbance was more common among patients in the anastrozole groups, whereas weight gain occurred more frequently among patients in the megestrol acetate groups. Weight increases of 5% or more and 10% or more were more common among megestrol acetate‐treated patients; moreover, patients in this group continued to gain weight over time.
CONCLUSIONS
Anastrozole, given in doses of 1 and 10 mg once daily, represents a well tolerated and effective therapeutic option for the treatment of postmenopausal women with advanced breast carcinoma who progress after tamoxifen treatment. Cancer 1997; 79:730‐9. © 1997 American Cancer Society.
The new aromatase inhibitor anastrozole, given in doses of 1 and 10 mg once daily, is well tolerated and represents an effective therapeutic option for the treatment of advanced breast carcinoma in postmenopausal women who progress after tamoxifen treatment