Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial

Henke, Michael; Laszig, Roland; Rübe, Christian; Schäfer, Ulrich; Haase, Klaus-Dieter; Schilcher, B.; Mose, Stephan; Beer, Karl; Bürger, Ulrich; Dougherty, Chris; Frommhold, H

doi:10.1016/s0140-6736(03)14567-9

Cited by 1,174 publications

(811 citation statements)

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“…65 In another trial of patients with head neck cancer receiving radiation therapy only, poorer progression-free survival was reported in patients randomized to the recombinant human erythropoietin arm. 66 Given the results of our studies demonstrating the expression of erythropoietin receptor and its ligand erythropoietin in prostate cancer cells, further investigations of the biology of erythropoietin-erythropoietin receptor in prostate cancer are warranted.…”

Section: Discussionmentioning

confidence: 96%

Erythropoietin and erythropoietin receptor expression in human prostate cancer

et al. 2005

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Erythropoietin is a hematopoietic cytokine that regulates the production of red blood cells. Erythropoietin is normally produced in the adult kidney in a hypoxia-inducible manner. The recombinant form of human erythropoietin is in clinical use for the prevention and treatment of anemia that is associated with cancer and its treatment with chemoradiation therapy. A series of recent studies from our laboratory and others have reported the expression of receptors for erythropoietin in several different types of human cancer cells. In the present study, we investigated the expression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer. In clinical specimens of prostate cancer, we found abundant expression of erythropoietin receptor protein in all primary tumors examined using immunohistochemistry. Furthermore, we observed erythropoietin coexpression in prostate cancer cells by immunohistochemical analysis. To determine whether monolayer cultures of continuous cell lines derived from prostate cancer also express erythropoietin receptor and erythropoietin, we studied well-characterized hormone-responsive (LNCaP) and hormone-refractory (PC-3) prostate cancer cell lines. We performed reverse-transcription and polymerase chain reaction assays to detect erythropoietin receptor and erythropoietin mRNA transcripts, and also immunoprecipitation and immunoblotting to detect erythropoietin receptor protein expression in prostate cancer cells. These experiments revealed the expression of both erythropoietin receptor and erythropoietin in LNCaP and PC-3 cells suggesting that these prostate cancer cell lines may serve as useful experimental models for further studies of erythropoietin and erythropoietin receptor function in prostate cancer. The coexpression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer cells suggests the potential for growth regulation by erythropoietin-erythropoietin receptor in an autocrine or paracrine manner.

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Section: Discussionmentioning

confidence: 96%

Erythropoietin and erythropoietin receptor expression in human prostate cancer

et al. 2005

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“…27 Moreover, recently, two prospective multicenter studies involving patients with breast carcinoma and patients with head and neck carcinoma have suggested that despite elevating hemoglobin levels, rHuEpo, compared with placebo, may have an adverse effect on overall prognosis. 28,29 Cellular responses to Epo may collectively promote the growth of EpoR-bearing tumors, and these actions may be enhanced further by either high levels of endogenous Epo production or by exogenous Epo administration. Therefore, until it has been clearly demonstrated that pharmacologic doses of Epo lack such trophic effects in vivo, we suggest that the administration of rHuEpo to treat patients with malignant disease should be performed with some degree of caution.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of erythropoietin expression in human endometrial carcinoma

Ács

Chu

et al. 2004

Cancer

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Objective To study whether the Disease Activity Score (DAS) is a valid measure of disease activity in undifferentiated arthritis (UA). Methods Data from a randomized, double‐blind, placebo‐controlled trial of methotrexate (MTX) and placebo involving 110 patients with UA were used. Data included baseline and 3, 6, 9, and 12 months, as well as diagnosis at 18 months. Validity of the DAS was analyzed using factor analysis, correlations with disease activity variables, correlations with changes in disability and joint damage, differences in DAS between diagnoses, and detecting the difference between placebo and MTX. Results Three disease activity factors were retrieved from the disease activity variables: patient reported outcomes, tender and swollen joints, and acute phase reactants. The DAS had its highest correlations (r > 0.77) with tender joint counts, followed by swollen joint counts (r > 0.63) and patient reported outcomes (r > 0.30), but the DAS correlated less with C‐reactive protein levels (r = 0.32). Over time, the DAS was related to the Health Assessment Questionnaire response with an odds ratio of 4.1 (95% confidence interval 2.1–8.0), but not with change in joint damage. At 18 months, the mean DAS was 2.6 for rheumatoid arthritis patients, 2.2 for UA patients, and 1.9 for patients in remission (P = 0.001). The DAS discriminated better than all single variables between MTX and placebo, with a Guyatt's effect size of 0.89. Conclusion The DAS appears to be a reasonably valid measure of disease activity for use in UA clinical trials.

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“…While the target hemoglobin levels were significantly more often reached in the treatment group, unfortunately the survival chances were significantly better in the placebo group. This latter finding is restricted to Strata 2 and 3 and could be explained by a stimulating effect of epoetin beta on the remaining tumor tissue (Henke et al, 2003). Using Cox regression analysis, Henke et al (2006) identified the c20 expression (erythropoietin receptor status) as a new biomarker for the prognosis of locoregional progression-free survival.…”

Section: The Epo Studymentioning

confidence: 98%

The Performance of Risk Prediction Models

Gerds¹,

Cai²,

2008

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SummaryFor medical decision making and patient information, predictions of future status variables play an important role. Risk prediction models can be derived with many different statistical approaches. To compare them, measures of predictive performance are derived from ROC methodology and from probability forecasting theory. These tools can be applied to assess single markers, multivariable regression models and complex model selection algorithms. This article provides a systematic review of the modern way of assessing risk prediction models. Particular attention is put on proper benchmarks and resampling techniques that are important for the interpretation of measured performance. All methods are illustrated with data from a clinical study in head and neck cancer patients.

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Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial

Cited by 1,174 publications

References 31 publications

Erythropoietin and erythropoietin receptor expression in human prostate cancer

Erythropoietin and erythropoietin receptor expression in human prostate cancer

Prognostic significance of erythropoietin expression in human endometrial carcinoma

The Performance of Risk Prediction Models

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