Epo (ESA) 和癌症 (「Z > B」)?

利大於弊 ?

Besides stimulating erythropoiesis, Epo has been shown to have both anti-apoptotic and pro-proliferative actions in endothelial cells, brain +/- spinal cord, kidney and heart. Furthermore, Epo has also been shown to promote angiogenesis in endothelial cells. These non-erythroid functions of Epo are not fully understood.

任何藥物都有利與弊，患者常會要求或是問他每週施打的Epo (ESA)劑量為多少？打少了還會抗議。然而，是不是打愈多的Epo愈好？是不是愈高的血色素(Hb)愈好？

過高的Hb會引起一些血栓性的疾病，所以在2010年FDA已下修Hb值為不要超過11 g/dl。
FDA Drug Safety Communication: Modified dosing recommendations to improve the safe use of Erythropoiesis-Stimulating Agents (ESAs) in chronic kidney disease

In controlled trials with CKD patients, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL.

[6-24-2011] http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm

然而，最近KI有篇文章整理了Epo和癌症的關係，因為Epo會引起血管新生(angiogenesis)，而這angiogenesis也是癌症是否惡化的關鍵因子。因此，建議有癌症病史的患者，Hb不要超過 10 g/dl，以免症狀惡化或是復發。

Kidney Int. 2014 Jul;86(1):34-9. 

Treatment with erythropoiesis-stimulating agents in chronic kidney disease patients with cancer.

Nephrology Literature on ESA usage in Patients with CKD and Cancer

• The TREAT trial was a landmark study in the field of nephrology which was published in 2009 in the NEJM. The TREAT (and CHOIR) trials changed how we treated anemia. In this study, more than 4000 diabetic CKD patients with anemia were randomized to either higher hemoglobin (Hb) target (13 g/dl) with darbepoetin or lower hb target (9 g/dl) in placebo arm. Surprisingly, there was a trend towards increased risk of death due to cancer in the Epo group (darbepoetin alfa group 39 deaths, placebo group 25 deaths, P=0.08). Also, in patients with a previous history of cancer, there was increased mortality due to malignancy in Epo group (darbepoeitin alpha 14/188 deaths, Control 1/160 deaths, P=0.002). 這是第一篇提醒我們Epo和癌症的相關性。

Clinical Implications and Recommendations for ESA use in Patients with CKD and Cancer 
1. The nondialysis CKD/ESRD patient with current cancer:

• Suggest generally limiting the Hb target to an upper level of 10 g/dl to prevent risk of stroke and mortality with higher Hb targets.

2. The nondialysis CKD/ESRD patient with a previous history of cancer:

• For up to 5 years after potential cure, treat with ESAs as if active cancer was present, maintaining an upper limit of Hb of 10 g/dl.