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

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

Bone marrow produces sufficient alloreactive natural killer (NK) cells in vivo to cure mice from subcutaneously and intravascularly injected 4T1 breast cancer

PURPOSE: Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases. METHODS: Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose–response relation. The potential of bone marrow as source of alloreactive NK cells was explored using MHC-mismatched mice as recipients of 4T1. Chemo-irradiation consisted of 2× 2 Gy total body irradiation and 200 mg/kg cyclophosphamide. Antibody-mediated in vivo NK cell depletion was applied to demonstrate the NK cell’s role. RESULTS: Administration of 2.5 instead of 5 million alloreactive NK cells significantly reduced PFS, evidencing dose responsiveness. Compared to MHC-matched receivers of subcutaneous 4T1, fewer MHC-mismatched mice developed tumors, which was due to NK cell alloreactivity because in vivo NK cell depletion facilitated tumor growth. Application of low-dose chemo-irradiation increased plasma levels of NK cell-activating cytokines, NK cell activity and enhanced NK cell-dependent elimination of subcutaneous tumors. Intravenously injected 4T1 was eliminated by alloreactive NK cells in MHC-mismatched recipients without the need for chemo-irradiation. CONCLUSIONS: Bone marrow is a suitable source of sufficient alloreactive NK cells for the cure of 4T1 breast cancer. These results prompt clinical exploration of bone marrow transplantation from NK-alloreactive MHC-mismatched donors in patients with metastasized breast cancer