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| Name | Class |
|---|---|
| Hospira, now a wholly owned subsidiary of Pfizer | INDUSTRY |
| Roche Pharma AG | INDUSTRY |
| Vifor Pharma | INDUSTRY |
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Anemia in patients with cancer is a common problem associated with an impaired quality of life.
Treatment with erythropoiesis stimulating agents (ESA) allows an increase in hemoglobin levels in 40-70% of patients and decreased transfusion requirements.
Absolute or functional iron deficiency is also common with about 30% of cancer patients with all histologies combined iron deficiency and anemia.
Several studies have shown the benefits of the combination of intravenous iron to erythropoiesis-stimulating agents in improving hemoglobin. However, none of them, to the investigators knowledge, has not been specifically performed on a population of patients with functional iron deficiency.
In addition, in clinical practice, this association is not carried out in particular because there is no dosage or consensus sequence for the administration of iron associated with ESAs.
- Iron Deficiency and Cancer The literature review therefore presents uncertainties do not allow the routine application of intravenous iron associated with ESAs. The SOR also conclude that IV iron is "consider" if iron deficiency.
These uncertainties are the heterogeneity of the study populations, contradictory results and the use of patterns intravenous iron binding and non-standardized.
The investigators focus in this study in patients with chemotherapy-induced anemia with functional iron deficiency is a cause of lack of response to ESA. Indeed, patients with true iron deficiency seems to justify a routine iron supplementation. In contrast, patients without iron deficiency do not warrant formal way of initiating such treatment (although the literature is contradictory).
This study aims to evaluate, in patients with chemotherapy-induced anemia and functional iron deficiency, the efficacy and safety of the combination epoietin zeta + Iron in concomitant intravenous or sequential.
Because data RCP (Summary of Product Characteristics), ease of use, its safety profile, the ability to achieve higher doses of iron with a lower frequency and with better adherence, the ferric carboxymaltose was chosen as an intravenous iron. One specialty is available, the Ferinject ® (Laboratoires VIFOR Pharma).
The erythropoiesis-stimulating agent chosen in this study is epoietin zeta.
- Hepcidin and iron Hepcidin is a peptide hormone of 25 amino acids produced by the liver and considered as the central regulator of iron homeostasis in the body.
It works by controlling intestinal iron absorption and iron reuse by the reticuloendothelial system. Hepcidin acts by preventing the export of iron enterocytes, intestinal site of absorption of dietary iron, and macrophages, iron recycling site of hemoglobin, by binding to ferroportin present at the membrane these cells and by inducing its internalization and degradation.
Accordingly, hepcidin can be considered a hyposidérémiante hormone. The hepcidin rate is increased by the iron thereby limiting its accumulation and tissue damage associated with iron overload. Inversely, the rate is reduced hepcidin during increased iron as anemia needs, hypoxia, pregnancy or other situations of iron deficiency.
Moreover, hepcidin is strongly induced by inflammation. Thus, in pathological situations such as cancer, high levels of hepcidin explain well enough inflammatory anemia characterized by anemia, iron retention at storage proteins such as ferritin but also at the level of the reticuloendothelial system endothelial and a decrease in intestinal iron absorption.
Despite its importance in the pathophysiology of anemia of inflammation and a fortiori with iron deficiency anemia functional hepcidin is not measured in clinical routine. There is not, to the investigators knowledge, prospective data on its blood levels in situations of iron deficiency anemia in cancer patients functional and data on changes in hepcidin levels induced by treatment with intravenous iron or with erythropoietin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Concomitant iron and I.V. epoietin zeta | Experimental |
| |
| Iron and I.V. epoietin zeta sequential | Experimental |
| |
| Epoietin zeta | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARM A : IV iron + epoietin zeta | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with hematopoietic response at 10 weeks. | The primary objective is to evaluate the rate of hematopoietic response to 10 weeks in patients with anemia and functional iron deficiency treated epoietin zeta + carboxymaltose concomitant IV iron, by epoietin zeta + carboxymaltose IV ferric sequential or epoietin zeta alone | The rate of hematopoietic response will be evaluated 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of transfusion requirements | The secondary objective is to assess transfusion requirements will be evaluated throughout the study | The number of transfusions will be evaluated weekly Week 1-16 |
| Measure | Description | Time Frame |
|---|---|---|
| The hematopoietic response at 6 and 16 weeks | The hematopoietic response will be evaluated at 6 and 16 weeks | |
| The time to achieve the therapeutic goal (hemoglobin> 12g/dl or increase in hemoglobin> 2g/dl) | The time to achieve the therapeutic goal will be determine 6,10 and 16 weeks after treatment start |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Emmanuel SEVIN, MD | Centre François Baclesse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU | Caen | 14000 | France | |||
| Centre François Baclesse |
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|
| ARM B: IV iron + epoietin zeta sequence | Drug |
|
|
| ARM C : single epoietin zeta | Drug | Epoietin zeta at a dose of 450 IU / kg per week subcutaneously begun in week 1 |
|
| Quality of life | Quality of life will be evaluated 6,10 and 16 weeks after treatment start |
| The consumption of erythropoiesis stimulating agent | The consumption of erythropoiesis stimulating agent will be evaluated 6,10 and 16 weeks after treatment start |
| The mean increase in hemoglobin concentration | The mean increase in hemoglobin concentration will be evaluated weekly Week 1-16 |
| The evolution of the iron status parameters | Ferritin, CST, soluble transferrin receptor, reticulocytes, CRP will be dosed at weeks 4,6,10,13 and 16 | The evolution of the iron status parameters will be performed at weeks 4,6,10,13 and 16 |
| Tolerance | Tolerance will be evaluated at weeks 6, 10 and 16 |
| Fatigue | Fatigue will be estimated with the generic scale FACT-G | Fatigue will be evaluated 6,10 and 16 weeks after treatment start |
| Caen |
| 14076 |
| France |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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