Question clinique Anémie et cancer, place de l'EPO  

Question clinique Anémie et cancer, place de l'EPO
ANÉMIE ET CANCER
PLACE POUR L’ÉRYTHROPOÏÉTINE?
ANTUNES, André
Médecine Interne
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11 février 2019

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Mr ,82 ans
Adénocarcinome de la vésicule biliaire métastatique sous forme de carcinose péritonéale
diagnostiqué 11.2018
TT: Nexium 20mg 1-0-0-0, Fluoxetine 20mg 0-0-0-1, Targin 40/20 1-0-0-1, Oxynorm en R
Chimiothérapie Oxaliplatine + Gemcitabine depuis 12.2018
Perte 6kgs sur 2 mois
Asthenie ++
Inappétence ++ (3 Fortimel/j)
LABO
Lc 10.5 G/L
Hb 91 g/l, Htc 0.27 L/L, Réticulocytes 20 G/L
MCH 29pg, MCV 88fL, MCHC 334g/l
Ferritine 1200 ug/L
Coeficient sat transferrine 8%
Folate 26.6nmol/L
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B12 1300 pmol/l

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Mr L., 82 ans
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ORIGINE DE L’ANÉMIE CHEZ CE PATIENT?

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Mr L., 82 ans
ORIGINE DE L’ANÉMIE CHEZ CE PATIENT?
ATTITUDE THÉRAPEUTIQUE?
A)1 CE
B)Fer i.v.
C)Fer p.o.
D)EPO
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E) Pause chimio, recontrôle labo dans 1 semaine

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ANÉMIE ET CANCER
UNE ASSOCIATION FRÉQUENTE
Figure 1 – Prévalence d’anémie ferriprive (iron deficiency anemia = ID) et anémie en di
Rev Braas Hematol Hemoter. 2016;38(4):325–330
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érents types de cancer.

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ANÉMIE ET CANCER
UNE ASSOCIATION FRÉQUENTE
SYMPTÔMES
Fatigue, adynamie, dyspnée d’e ort;
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Baisse du niveau de performance physique;
Malaise.
CONSÉQUENCES
Baisse de la réserve physiologique;
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Baisse de la qualité de vie (QoL).

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ANÉMIE ET
CANCER
ANÉMIE CHEZ PATIENTS ATTEINTS
DE CANCER
PHYSIOPATHOLOGIE
CANCER
INFLAMMATION
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++ CYTOKINES (IL-6)
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++ HEPCIDINE
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- FERROPORTINE
DIMINUTION DE L’ABSORTION
INTESTINALE DE FER
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Fer p.o.
Fer p.o.
TRAITEMENT
MYÉLOSUPPRESSION
HÉMOLYSE
HÉMORRAGIE
DÉFICIT NUTRIONNEL
CARENCE MARTIALE, DE
FOLATE ET DE VIT. B12
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1.
N Engl J Med 2005;352:1011-23

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ANÉMIE ET CANCER
ANÉMIE CHEZ PATIENTS ATTEINTS DE CANCER
PHYSIOPATHOLOGIE
CANCER
INFLAMMATION
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++ CYTOKINES (IL-6)
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++ HEPCIDINE
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- FERROPORTINE
DIMINUTION DE L’ABSORTION
INTESTINALE DE FER
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Fer p.o.
TRAITEMENT
MYÉLOSUPPRESSION
HÉMOLYSE
HÉMORRAGIE
DÉFICIT NUTRIONNEL
CARENCE MARTIALE, DE
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FOLATE ET DE VIT. B12

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ANÉMIE ET CANCER
ANÉMIE CHEZ PATIENTS ATTEINTS DE CANCER
PHYSIOPATHOLOGIE
PÉRTURBATION
DE L'ÉRYTHROPOÏÈSE
ET DE LA DISPONIBILITÉ DU FER
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ANÉMIE TYPIQUEMENT LÉGÈRE
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Hg ~ 10 g/dL

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ANÉMIE ET CANCER
ANÉMIE CHEZ PATIENTS ATTEINTS DE CANCER EN COURS DE CHIMIOTHÉRAPIE
TRAITEMENT
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ESA
FER I.V.
CE

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ANÉMIE ET CANCER
ANÉMIE CHEZ PATIENTS ATTEINTS DE CANCER EN COURS DE CHIMIOTHÉRAPIE
TRAITEMENT
ESA
FER I.V.
CE
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r-HuEpo
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Erythropietin Stimulating Factor

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ANÉMIE ET CANCER
J Formos Med Assoc.
L’UTILISATION DE L’R-HUEPO
Image_350_0
EPO
Rein (>80%)
Foie (10-40%)
SNC (inconnu)
Testicules
Rate
Figure 2 – Rôle de l’EPO dans la di
érenciation érythroïde.
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 2018 Nov;117(11):955-963.

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
Hémoglobine
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Figure 3 – Concentration d’Hémoglobine (Hb) au cours de la période de traitement.
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J Clin Oncol (2006) 24:2290-2297

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
Hémoglobine
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Transfusions
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Figure 4 – Percentage de patients atteints des maladies lymphoprolifératives
sous ESA vs Controls qui ont reçu des CE
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Leukemia & Lymphoma, November 2012; 53(11): 2151–2158

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
“We found that ESAs provide a small but
Hémoglobine
clinically important improvement in
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Transfusions
QoL
anaemia-related symptoms (FACT-An).”
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British Journal of Cancer (2014) 111, 33–45
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Cochrane Database of Systematic Reviews 2012, Issue 12.

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
Mortalité et progression tumorale augmentés?
Overall, there is currently no clinical evidence (neither
single studies nor metaanalyses) indicating an e ect of
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ESAs on stimulating disease progression or relapse
when used within label and following recommendations
for the treatment of CIA [I, A]”
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Cochrane Database of Systematic Reviews 2012, Issue 12.

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
Image_350_0
ESA
Survie et
progression/
réponse
tumorale
=
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Cochrane Database of Systematic Reviews 2012, Issue 12.

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
Image_350_0
ESA
RISQUE DE THROMBOSE
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British Journal of Cancer (2010) 102(2), 301 – 315
RISQUE DE THROMBOPENIE/ HEMORRAGIE et de HTA
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Cochrane Database of Systematic Reviews 2012, Issue 12.

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ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
ESA ET RISQUE DE THROMBOSE
FACTEURS DE RISQUE DE THROMBOSE VEINEUSE
Hématocrite élevé
Âge
Immobilisation prolongée
Néoplasie
Chirurgie majeure
Politraumatisme
TV auparavant
Insu sance cardiaque chronique
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Traitements immunomodulateurs

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ANTICOAGULATION
ANÉMIE ET CANCER
L’UTILISATION DE L’R-HUEPO
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ESA
ESA ET RISQUE DE THROMBOSE
FACTEURS DE RISQUE DE THROMBOSE VEINEUSE
Hématocrite élevé
Âge
Immobilisation prolongée
Néoplasie
Chirurgie majeure
Politraumatisme
TV auparavant
Insu sance cardiaque chronique
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Traitements immunomodulateurs
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PAS
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RECOMMANDÉE

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ANÉMIE ET CANCER
r-HuEpo en Suisse
TRAITEMENT
L’UTILISATION DE L’R-HUEPO
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ESA
ARANESP®
(DARBÉPOÉTINE
500ug/3 semaines
ou
2.25 ug/kg/semaine
COÛT DU
2600 chf
6 SEMAINES
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RECORMON®
(ÉPOÉTINE BETA)
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30000 IU/semaine
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2200 chf
EPREX®
(ÉPOÉTINE ALFA)
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450 IU/kg/semaine ou
150IU/kg 3x/semaine
2200chf
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MIRCERA®
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(Methoxy
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polyethylene glycol-
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epoietine-beta)
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EPOTHETA-TEVA®
(ÉPOÉTINE THETA)
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20000 IU/semaine
(double dose possible)
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1200chf

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ANÉMIE ET CANCER
ESA
Indications:
Contre-Indications:
1. HTA mal controlée
II. Hb>12g/dl
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III. Risque thrombotique

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Même si
asymptomatique
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ESA si patient
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symptomatique

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ANÉMIE ET CANCER
POINTS CLÉ
ESA
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(R-HuEPO)

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BIBLIOGRAPHIE
1.
2.
3.
4.
5.
6.
7.
8.
9.
Goodnough LT; Weiss G: Anemia of Chronic Disease: N Engl J Med 2005;352:1011-23
Naoum FA ; Iron deficiency in cancer patients; Rev Bras Hematol Hemoter; 2016; 38(4):325–330
Shih HM; Wu CJ; Lin SL; Physiology and pathophysiology of renal erythropoietin-producing cells;
J Formos Med Assoc.; 2018 Nov; 117(11):955-963
Lai SY, Grandis JR; Understanding the presence and function of erythropoietin receptors on
cancer cells; J Clin Oncol 2006; 24: 4675 – 4676
Hedenus M; Osterborg A; Coi er B; E ects of erythropoiesis-stimulating agents on survival and
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other outcomes in patients with lymphoproliferative malignancies: a study-level meta-analysis;
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Leukemia & Lymphoma; November 2012; 53(11): 2151–2158
Erythropoietin or darbepoetin for patients with cancer; Cochrane Database of Systematic
Reviews 2012, Issue 12.
Glaspy J; Crawford J et al; Erythropoiesis-stimulating agents in oncology: a study-level meta-
analysis of survival and other safety outcomes; British Journal of Cancer 2010;102:301-15
Aapro M; Beguin Y et al; Management of anemia and iron deficiency in patients with cancer:
ESMO Clinical Practice Guidelines; Annals of Oncology 29 : iv96-iv110, 2018
Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer:
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uptodate
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