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

Beijer, Sandra; Rossum, Erik van; Hupperets, P.; Spreeuwenberg, Cor; Beuken, Marieke van den; Winkens, Ron; Ars, Lisette; Borne, B.E. van den; Graeff, Alexander de; Dagnelie, Pieter C.

doi:10.1186/1471-2458-7-4

Cited by 8 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, this aspect should be taken into due consideration for future clinical application of these compounds, as the failure of cell duplication in normal tissues might cause possible broader side effects. So far, ATP has been used as a compassionate drug in terminally ill patients [68,69]. The systemic administration did not cause important side effects indicating that the therapy with this compound may be tolerated [70].…”

Section: Discussionmentioning

confidence: 99%

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells

D’Alimonte

Nargi

Zuccarini

et al. 2015

Purinergic Signalling

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM), the most common and aggressive brain tumor in humans, comprises a population of stem-like cells (GSCs) that are currently investigated as potential target for GBM therapy. Here, we used GSCs isolated from three different GBM surgical specimens to examine the antitumor activity of purines. Cultured GSCs expressed either metabotropic adenosine P1 and ATP P2Y receptors or ionotropic P2X7 receptors. GSC exposure for 48 h to 10-150 μM ATP, P2R ligand, or to ADPβS or MRS2365, P2Y1R agonists, enhanced cell expansion. This effect was counteracted by the PY1R antagonist MRS2500. In contrast, 48-h treatment with higher doses of ATP or UTP, which binds to P2Y2/4R, or 2'(3')-O-(4-benzoylbenzoyl)-ATP (Bz-ATP), P2X7R agonist, decreased GSC proliferation. Such a reduction was due to apoptotic or necrotic cell death but mostly to growth arrest. Accordingly, cell regrowth and secondary neurosphere formation were observed 2 weeks after the end of treatment. Suramin, nonselective P2R antagonist, MRS1220 or AZ11645373, selective A3R or P2X7R antagonists, respectively, counteracted ATP antiproliferative effects. AZ11645373 also abolished the inhibitory effect of Bz-ATP low doses on GSC growth. These findings provide important clues on the anticancer potential of ligands for A3R, P2Y1R, and P2X7R, which are involved in the GSC growth control. Interestingly, ATP and BzATP potentiated the cytotoxicity of temozolomide (TMZ), currently used for GBM therapy, enabling it to cause a greater and long-lasting inhibitory effect on GSC duplication when readded to cells previously treated with purine nucleotides plus TMZ. These are the first findings identifying purine nucleotides as able to enhance TMZ antitumor efficacy and might have an immediate translational impact.

show abstract

Section: Discussionmentioning

confidence: 99%

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells

D’Alimonte

Nargi

Zuccarini

et al. 2015

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…The present study was part of a randomized clinical trial aimed at evaluating the effects of ATP infusions over 8 weeks ( versus no ATP) on QoL, fatigue, and physical restriction in preterminal cancer patients 21. Baseline measurements were used to assess several QoL domains, symptoms and overall QoL in a cross‐sectional design.…”

Section: Patient and Methodsmentioning

confidence: 99%

Determinants of overall quality of life in preterminal cancer patients

Beijer

Kempen

Pijls‐Johannesma

et al. 2008

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Recently, a few studies reported that fatigue was a predominant contributor to patient-perceived overall QoL in patients with different types of cancer in a relatively early stage of disease. In the present study, we aimed to investigate whether fatigue is also a major contributor to overall QoL in preterminal cancer patients. Ninety-eight preterminal cancer patients, mainly lung (44%) and gastrointestinal cancer (25%), with an estimated life expectancy of 1-6 months were included. QoL domains as well as overall QoL were measured using the EORTC QLQ-C30 questionnaire. Data were analysed by Pearson's correlations and multivariate modelling. Fatigue showed the strongest correlation with overall QoL (r = -0.63, p < 0.001), followed in decreasing order by role functioning (r = 0.53), physical functioning (r = 0.47), social functioning (r = 0.44), nausea (r = -0.37), cognitive functioning (r = 0.33), appetite loss (r = -0.31), dyspnea (r = -0.26) and emotional functioning (r = 0.24). Multivariate analysis confirmed that the fatigue scale paid by far the highest individual contribution to overall QoL (standardized regression coefficient (SRC): -0.41, p = 0.002), followed by social functioning (SRC: 0.18, p = 0.05). None of the other domains or symptom scales contributed independently to overall QoL. Our results clearly demonstrate that, in preterminal cancer patients, fatigue is a major contributor of overall QoL, corroborating reports in cancer patients in earlier disease stages.

show abstract

“…The study was approved by the Ethical Committee of University Hospital Maastricht and Maastricht University, and all patients signed written informed consent prior to the study. Details of the trial design have been published elsewhere [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2007

Self Cite

View full text Add to dashboard Cite

Summary 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.

show abstract

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

Cited by 8 publications

References 23 publications

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells

Determinants of overall quality of life in preterminal cancer patients

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

Contact Info

Product

Resources

About