Randomized, Double-Blind, Placebo-Controlled Trial of Erythropoietin in Non–Small-Cell Lung Cancer With Disease-Related Anemia

Wright, James R.; Ung, Yee C.; Julian, Jim A.; Pritchard, Kathleen I.; Whelan, Timothy J.; Smith, Colleen; Szechtman, Barbara; Roa, Wilson; Mulroy, Liam; Rudinskas, Leona; Gagnon, Bruno; Okawara, G.; Levine, Mark

doi:10.1200/jco.2006.07.1514

Cited by 393 publications

(247 citation statements)

References 26 publications

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“…Several placebo-controlled randomized controlled phase III trials were initiated to test this strategy, or to test EPO in combination with chemotherapy, and the outcome was a surprise. Despite a demonstrable improvement in hemoglobin concentration after EPO [5], the trials consistently found a worse tumor outcome in the EPO arm [6][7][8][9][10]. The biological mechanism behind this unexpected finding remains controversial [11] although it is likely the result of EPO acting as a survival/growth factor for cancer cells expressing erythropoietin surface receptors…”

Section: Evidence-based Medicine and Randomized Controlled Trialsmentioning

confidence: 99%

Randomized controlled trials in health technology assessment: Overkill or overdue?

Bentzen

2008

Radiotherapy and Oncology

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Evidence-based medicine has become a cornerstone in the development of radiation oncology and the randomized controlled phase III trial remains the gold standard for assessing differential benefits in clinical outcome between therapies. Health technologies aimed at improving treatment quality should primarily be tested using process measures or operational characteristics, the reason being that the sensitivity and specificity of clinical outcome is low for detecting quality improvements. The ongoing discussion of the relative merits of intensity modulated photon vs. proton radiotherapy is used to illustrate these concepts. Concerns over clinical and individual equipoise as well as the potential limitations of health economics considerations in this setting are also discussed. Working in a technology and science based medical discipline, radiation oncology researchers need to further develop methodology for critical assessment of health technologies as a complement to randomized controlled trials."Only two options exist. The first is that we accept that, under exceptional circumstances, common sense might be applied when considering the potential risks and benefits of interventions. The second is that we continue our quest for the holy grail of exclusively evidence based interventions and preclude parachute use outside the context of a properly conducted trial." Evidence-based medicine and randomized controlled trialsEvidence-based medicine is a compelling paradigm as a rational road-map, some would argue the only rational road-map, for improving the standard of health care [2,3]. The role of randomized controlled trials in this context cannot be overstated: while the allocation to different treatment options may be skewed even in a specific randomized trial, randomization is the only method that on average safe-guards against prognostic imbalances that could bias therapy effect estimates. History shows, that even when there has been overwhelming support for a novel therapeutic intervention in terms of a well-proven mechanism of action, promising pre-clinical and early clinical data as well as wide-spread consensus regarding an expected benefit among the experts, the cold-hearted scrutiny of a,

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Section: Evidence-based Medicine and Randomized Controlled Trialsmentioning

confidence: 99%

Randomized controlled trials in health technology assessment: Overkill or overdue?

Bentzen

2008

Radiotherapy and Oncology

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“…[5] However, similar to the aforementioned articles, there were no findings of mesenteric thrombosis as a thrombotic complication of erythropoiesis-stimulating drugs. [3–13]…”

Section: Discussionmentioning

confidence: 99%

“…This report is the first case of mesenteric infarction due to iatrogenic polycythemia in the literature. [3–13]…”

Section: Introductionmentioning

confidence: 99%

Mesenteric infarction due to iatrogenic polycythemia

Skoog¹,

Carmelle-Elie²,

Ferguson³

2013

World Journal of Emergency Medicine

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BACKGROUND:Polycythemia vera is defined as a chronic myeloproliferative disorder characterized by increased red blood cell count. There have been no reports on mesenteric thrombosis resulting from iatrogenic polycythemia.METHODS:We present a patient with a history of non-small cell lung cancer undergoing maintenance oral chemotherapy on tarceva and adjunctive use of procrit. The patient presented to our emergency department with an acute abdomen and was found to have ischemic bowel from unmonitored procrit, which lead to hyperviscosity of blood and mesenteric infarction.RESULTS:The patient remained intubated with ventilator support. He refused a tracheostomy. He continued on feeding through the J port of the nasojejunal tube. His white cell count, and hematocrit and creatinine levels remained normal. Procrit use and chemotherapy were not restarted. He was transferred to a subacute nursing facility for further treatment.CONCLUSIONS:Procrit and other erythropoiesis stimulating drugs can cause significant morbidity and mortality with an increased risk of cardiovascular events, gastrointestinal bleeding, thromboembolism and stroke. This case report suggests that without closely monitoring hematocrit levels, epoetin may also be associated with an increased risk of mesenteric infarction.

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“…However, the conflicting effects of ESAs were recently described in distinct studies [70][71][72]. Indeed, besides cardiovascular and thromboembolic events in erythropoietin-treated patients, several phase II and III trials showed a significant deterioration of cancer patients survival [73][74][75].…”

Section: Deregulation Of Erythropoiesis By Tnfα α α α In Inflammationmentioning

confidence: 99%

Linking anemia to inflammation and cancer: The crucial role of TNFα

Buck

Morceau

Grigorakaki

et al. 2009

Biochemical Pharmacology

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Erythropoiesis is considered as a multistep and tightly regulated process under the control of a series of cytokines including erythropoietin (Epo). Epo activates specific signaling pathways and leads to activation of key transcription factors such as GATA-1, in order to ensure erythroid differentiation. Deregulation leads to a decreased number of red blood cells, a hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood. Anemia represents a frequent complication in various diseases such as cancer or inflammatory diseases. It reduces both quality of life and prognosis in patients. Tumor necrosis factor alpha (TNFα) was described to be involved in the pathogenesis of inflammation and cancer related anemia. Blood transfusions and erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are currently used as efficient treatments. Moreover, the recently described conflicting effects of ESAs in distinct studies require further investigations on the molecular mechanisms involved in TNFα-caused anemia. The present study aims to evaluate the current knowledge and the importance of the effect of the proinflammatory cytokine TNFα on erythropoiesis in inflammatory and malignant conditions.

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Randomized, Double-Blind, Placebo-Controlled Trial of Erythropoietin in Non–Small-Cell Lung Cancer With Disease-Related Anemia

Cited by 393 publications

References 26 publications

Randomized controlled trials in health technology assessment: Overkill or overdue?

Randomized controlled trials in health technology assessment: Overkill or overdue?

Mesenteric infarction due to iatrogenic polycythemia

Linking anemia to inflammation and cancer: The crucial role of TNFα

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