Early stopping of clinical trials

Early stopping of clinical trials in favour of a new treatment creates ethical and scientific difficulties, which are different from those associated with early stopping due to toxicity or futility. Two major breast cancer trials have recently taken such a decision, and the problem is relevant for several ongoing trials. Here we argue that such a decision should be taken with the utmost gravity and should be based on a clear overall clinical benefit for the new treatment, and not as an automatic response to crossing a predefined threshold. Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee (IDMC) about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation

Clinical trial update: National Cancer Institute of Canada

The Breast Cancer Site Group (BCSG) of the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) has conducted a wide variety of clinical trials focussing on large phase III trials of adjuvant chemotherapy, adjuvant hormonal therapy, and optimal delivery of adjuvant radiation therapy. The Group has also fostered, together with the NCIC CTG Investigational New Drug (IND) Program, a series of phase II and phase I/II studies which will be carried through if possible, into the phase III setting

8th International Conference: Primary Therapy of Early Breast Cancer, St Gallen, Switzerland, March 12–15 2003

The International St Gallen Breast Cancer Conference concentrates almost exclusively on adjuvant, multimodal primary therapy for early breast cancer. Begun 25 years ago, this meeting was initially held every 4 years, but therapeutic progress, new strategies and provocative trials data have accelerated to the extent that conferences are now held biennially. The meeting this year was attended by almost 3000 delegates. Major topics included new prognostic and predictive markers in early breast cancer, the best use of adjuvant chemotherapy and endocrine therapy, and innovations in local surgery and radiation therapy

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

Tamoxifen: the drug that came in from the cold

Despite the perception of many oncologists that tamoxifen is an inferior drug, and should be substituted by an aromatase inhibitor in post-menopausal women, the current evidence strongly supports the view that AIs should be used 2–3 years after tamoxifen to achieve the maximal overall survival (OS) advantage

Health care costs for the treatment of breast cancer recurrent events: estimates from a UK-based patient-level analysis

Cost pressures and the need to demonstrate cost-effectiveness of new interventions require consideration of the costs of treating disease. This study presents analyses of resource use data covering 199 postmenopausal women who experienced a breast cancer recurrent event between 1991 and 2004 and were treated at the Western General Hospital, Edinburgh. Aggregate (5-year) treatment costs for alternative recurrent events were estimated, as well as the annual costs incurred by patients experiencing contralateral, locoregional, or distant recurrence, who remained alive without further recurrence for a year. The 95% confidence intervals for the 5-year costs of recurrence ranged from £10 000 to £37 000 for locoregional recurrence, and £14 500–£20 000 for distant recurrence. No evidence of significant variations in these costs across time periods between 1991 and 2004 was identified. Annual costs for patients remaining in the same health state showed high initial costs for contralateral and locoregional recurrence, with low costs in subsequent years, while costs associated with distant recurrence declined at a slower rate and plateaued at 4–5 years post-diagnosis. The cost estimates presented in this paper not only inform the magnitude of the resource consequences of breast cancer recurrences, but they are also better suited to informing cost-effectiveness analyses, which have a far greater role in allocating health-care resources

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

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

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands

Background The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods In 45,229 surgically treated stage I–IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. Results Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4–2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6–14.8) when <35 to 1.5 (95% CI 1.4–1.7) for ≥60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48–0.69) and chemotherapy (HR 0.73; 95% CI 0.60–0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33–1.56). Conclusion Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection