Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients

The aim of the study was to investigate the safety of adenosine 5′-triphosphate (ATP) administration at home in pre-terminal cancer patients. Included were patients with cancer for whom medical treatment options were restricted to supportive care, who had a life expectancy of less than 6 months, a World Health Organization performance status 1 or 2, and suffered from at least one of the following complaints: fatigue, anorexia or weight loss >5% over the previous 6 months. Side effects were registered systematically on a standard form according to the National Cancer Institute (NCI) Common Toxicity Criteria. Fifty-one patients received a total of 266 intravenous ATP infusions. Of these, 11 infusions (4%) were given at the lowest dose of 20 μg kg−1 min−1, 85 infusions (32%) at 25–40 μg kg−1 min−1, and 170 (64%) at the highest dose of 45–50 μg kg−1 min−1 ATP. The majority of ATP infusions (63%) were without side effects. Dyspnea was the most common side effect (14% of infusions), followed by chest discomfort (12%) and the urge to take a deep breath (11%). No symptoms of cardiac ischemia occurred in any of the infusions. All side effects were transient and resolved within minutes after lowering the ATP infusion rate. Side effects were most frequent in the presence of cardiac disorders. We conclude that ATP at a maximum dose of 50 μg kg−1 min−1 can be safely administered in the home setting in patients with pre-terminal cancer

Application of adenosine 5'-triphosphate (ATP) infusions in palliative home care: design of a randomized clinical trial

BACKGROUND: Palliative care in cancer aims at alleviating the suffering of patients. A previous study in patients with advanced non-small-cell lung cancer showed that adenosine 5'-triphosphate (ATP) infusions had a favourable effect on fatigue, appetite, body weight, muscle strength, functional status and quality of life. The present study was designed 1. To evaluate whether ATP has favourable effects in terminally ill cancer patients, 2. To evaluate whether ATP infusions may reduce family caregiver burden and reduce the use of professional health care services, and 3. To test the feasibility of application of ATP infusions in a home care setting. METHODS/DESIGN: The study can be characterized as an open-labelled randomized controlled trial with two parallel groups. The intervention group received usual palliative care, two visits by an experienced dietician for advice, and regular ATP infusions over a period of 8 weeks. The control group received palliative care as usual and dietetic advice, but no ATP. This paper gives a description of the study design, selection of patients, interventions and outcome measures. DISCUSSION: From April 2002 through October 2006, a total of 100 patients have been randomized. Follow-up of patients will be completed in December 2006. At the time of writing, five patients are still in follow up. Of the 95 patients who have completed the study, 69 (73%) have completed four weeks of follow-up, and 53 (56%) have completed the full eight-week study period. The first results are expected in 2007

Improving the quality and efficiency of follow-up after curative treatment for breast cancer – rationale and study design of the MaCare trial

BACKGROUND: After curative treatment for breast cancer women frequently attend scheduled follow-up examinations. Usually the follow-up is most frequent in the first 2–3 years (2–4 times a year); thereafter the frequency is reduced to once a year in most countries. Its main aim is to detect local disease recurrence, or a second primary breast cancer, but also to provide information and psychosocial support. However, the cost-effectiveness of these frequent visits is under much debate, leading to a search for less intensive and more cost-effective follow-up strategies. In this paper the design of the MaCare trial is described. This trial compares the cost-effectiveness of four follow-up strategies for curatively treated breast cancer patients. We investigate the costs and effects of nurse-led telephone follow-up and a short educational group programme. METHODS/DESIGN: The MaCare trial is a multi centre randomised clinical trial in which 320 breast cancer patients are randomised into four follow-up strategies, focussed on the first 18 months after treatment: 1) standard follow-up; 2) nurse-led telephone follow-up; 3) arm 1 with the educational group programme; 4) arm 2 with the educational group programme. Data is collected at baseline and 3, 6, 12 and 18 months after treatment. The primary endpoint of the trial is cancer-specific quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30. Secondary outcomes are perceived feelings of control, anxiety, patients' satisfaction with follow-up and costs. A cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: Reduced follow-up strategies for breast cancer have not yet been widely applied in clinical practice. Improvement of psychosocial support and information to patients could lead to a better acceptance of reduced follow-up. The MaCare trial combines a reduced follow-up strategy with additional psychosocial support. Less frequent follow-up can reduce the burden on medical specialists and costs. The educational group programme can improve QoL of patients, but also less frequent follow-up can improve QoL by reducing the anxiety experienced for each follow-up visit. Results of the trial will provide knowledge on both costs and psychosocial aspects regarding follow-up and are expected in 2009

High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

BACKGROUND: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes. METHODS: Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes. Patients in the conventional-dose group received fluorouracil, epirubicin, and cyclophosphamide (FEC) every three weeks for five courses, followed by radiotherapy and tamoxifen. The high-dose treatment was identical, except that high-dose chemotherapy (6 g of cyclophosphamide per square meter of body-surface area, 480 mg of thiotepa per square meter, and 1600 mg of carboplatin per square meter) with autologous peripheral-blood hematopoietic progenitor-cell transplantation replaced the fifth course of FEC. RESULTS: Of the 885 patients, 442 were assigned to the high-dose group and 443 to the conventional-dose group. After a median follow-up of 57 months, the actuarial 5-year relapse-free survival rates were 59 percent in the conventional-dose group and 65 percent in the high-dose group (hazard ratio for relapse in the high-dose group, 0.83; 95 percent confidence interval, 0.66 to 1.03; P=0.09). In the group with 10 or more positive nodes, the relapse-free survival rates were 51 percent in the conventional-dose group and 61 percent in the high-dose group (P=0.05 by the log-rank test; hazard ratio for relapse, 0.71; 95 percent confidence interval, 0.50 to 1.00). CONCLUSIONS: High-dose alkylating therapy improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes. This benefit may be confined to patients with HER-2/neu-negative tumor

Randomized, Phase III Trial of Sequential Epirubicin and Docetaxel Versus Epirubicin Alone in Postmenopausal Patients With Node-Positive Breast Cancer

Purpose The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer. Patients and Methods After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI x 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study. The primary end point was disease-free survival (DFS). Results From 1997 to 2005, 803 patients entered DEVA (EPI x 6, n = 397; EPI-DOC, n = 406). At a median follow-up of 64.7 months (interquartile range, 45.2 to 84.4 months), 198 DFS events had been reported (EPI x 6, n = 114; EPI-DOC, n = 84). The 5-year DFS rates were 72.7% (95% CI, 68.0% to 77.3%) for epirubicin alone and 79.5% (95% CI, 75.2% to 83.8%) for epirubicin followed by docetaxel; evidence of improvement in DFS was observed with EPI-DOC (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.91; P = .008). One hundred twenty-seven patients have died (EPI x 6, n = 75; EPI-DOC, n = 52); a reduction in deaths was observed with EPI-DOC (HR, 0.66; 95% CI, 0.46 to 0.94; P = .02). The 5-year overall survival rates were 81.8% (95% CI, 77.7% to 85.9%) for epirubicin and 88.9% (95% CI, 85.5% to 92.2%) for epirubicin followed by docetaxel. Assessment of toxicity and QOL showed that EPI-DOC was associated with greater toxicity but with no difference in QOL between arms during follow-up. Conclusion These results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal women with node-positive, early breast cancer compared with six cycles of epirubicin monotherapy. J Clin Oncol 29:3247-3254. (C) 2011 by American Society of Clinical Oncolog

The devil is in the detail:quantifying vocal variation in a complex, multi-levelled, and rapidly evolving display

E.C.G. was funded by a Royal Society Newton International Fellowship. L.R. was supported by the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) and their support is gratefully acknowledged. MASTS is funded by the Scottish Funding Council (Grant Reference No. HR09011) and contributing institutions. Some funding and logistical support was provided to M.M.P. by the National Oceanic Society (USA), Dolphin & Whale Watching Expeditions (French Polynesia), Vista Press (USA), and the International Fund for Animal Welfare (via the South Pacific Whale Research Consortium).Identifying and quantifying variation in vocalizations is fundamental to advancing our understanding of processes such as speciation, sexual selection, and cultural evolution. The song of the humpback whale (Megaptera novaeangliae) presents an extreme example of complexity and cultural evolution. It is a long, hierarchically structured vocal display that undergoes constant evolutionary change. Obtaining robust metrics to quantify song variation at multiple scales (from a sound through to population variation across the seascape) is a substantial challenge. Here, we present a method to quantify song similarity at multiple levels within the hierarchy. To incorporate the complexity of these multiple levels, the calculation of similarity is weighted by measurements of sound units (lower levels within the display) to bridge the gap in information between upper and lower levels. Results demonstrate that the inclusion of weighting provides a more realistic and robust representation of song similarity at multiple levels within the display. Our method permits robust quantification of cultural patterns and processes that will also contribute to the conservation management of endangered humpback whale populations, and is applicable to any hierarchically structured signal sequence.PostprintPeer reviewe