Recombinant Human Erythropoietins and Cancer Patients: Updated Meta-Analysis of 57 Studies Including 9353 Patients

Abstract

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Mesenteric infarction due to iatrogenic polycythemia

“…Within this, the relative risk of a thrombo-embolic event was increased by 67% in the treated group compared with the control group ( RR =1.67, 95% CI =1.35 to 2.06). [5] However, similar to the aforementioned articles, there were no findings of mesenteric thrombosis as a thrombotic complication of erythropoiesis-stimulating drugs. [3–13]…”

High expression levels of erythropoietin and its receptor are not correlated with shorter survival in human glioblastoma

“…While certain studies observed beneficial effects (16)(17)(18), a lower survival rate was found in head-and-neck and breast cancer (22,23). apart from unclear effects on the tumor growth itself, systemic side effects including deep venous thrombosis or arterial hypertension may have worsened the patient outcome (24).…”

Eisenmangel, Thrombozytose und Thromboembolie

“…Eine Eisenersatztherapie ist die wichtigste therapeutische Maßnahme bei der krebsassoziierten Anämie; aufgrund der hepcidinbedingten Eisenverwertungsstörung ist allerdings das Ansprechen oft eingeschränkt, sodass eine begleitende Erythropoetintherapie, insbesondere bei der Chemotherapie-assoziierten Anämie, häufig notwendig wird [89,90]. Ein erhöhtes Thromboserisiko (RR 1,67) unter Erythropoese-stimulierenden Agenten stellt auch bei Malignompatienten ein erhebliches Problem dar [91]. Wie bei der renalen Anämie verursacht Erythropoetin einen funktionellen Eisenmangel, sodass eine begleitende Eisentherapie benötigt wird, um ein optimales Ansprechen zu erzielen [92,93].…”