Journal of Leukemia
Open Access

Brief Note on Erythropoietin Drug in Cancer

Meles Ahmed^{* *}Correspondence: Dr. Meles Ahmed, Department of Hematology, Jimma University, Jimma, Ethiopia, Email:

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Description

Anaemia develops during treatment in about 54% of initially non-anaemic cancer patients, caused by either the cancer itself or by the cytotoxic treatment. Before the advent of recombinant human erythropoietin (rHuEpo), blood transfusion was the only treatment option available for severe cancer-related anaemia. Three different Erythropoiesis Stimulating Agents (ESAs) are now available for the treatment of cancer patients: epoetin alpha, epoetin beta and darbepoetin alpha. The term epoetin is referred to both epoetin alpha and beta. Multiple studies and subsequent meta-analysis have demonstrated that ESA treatment can successfully increase haemoglobin levels and reduce the likelihood of transfusion. Randomized controlled studies in cancer patients undergoing chemotherapy have supported the notion that ESAs might improve tumour control or overall survival.

However, randomized clinical trials and systematic reviews of available clinical trials have demonstrated an increased risk of thromboembolism in patients receiving epoetin or darbepoetin. In fact, the sustained dose-dependent rise in haematocrit produced by Epo effectively abolishes the symptoms of anaemia, but at the cost of an increased blood viscosity.

Although ESAs have been employed for many years, results from several recent clinical trials have raised concerns that ESAs may have direct tumour-stimulating effects and promote tumour progression in anaemic cancer patients. While the safety of ESAs is now being debated, no prospective randomized trials have yet been conducted that adequately testing blood transfusions as an alternative approach to managing anaemia, or assessing the risks of transfusion in terms of safety and cost.

As Epo is frequently used in oncology practice to treat chemotherapy-induced anaemia in patients with cancer, a better understanding of in vitro and in vivo Epo and Epo receptor (EpoR) interactions in various types of cancer is of extreme importance. The effect of Epo on the survival rate of cancer patients is variable but it seems plausible that it might confer a survival benefit. A meta-analysis of 60 relevant studies found that anaemia increased the relative risk of death by 19% in lung cancer, 75% in head and neck cancer, 47% in prostate cancer, and 67% in lymphoma, and was associated with an overall estimated increased risk of death by 65%.

Three studies showed a statistically significant worse survival associated with the administration of Epo. In fact, Epo decreases the survival rate of patients with head and neck cancer, metastatic breast cancer, lymphoproliferative malignancies and advanced non-small-cell lung cancer. In patients with head and neck cancer, the negative survival effects seemed to be confined to patients with EpoRpositive tumors only. In fact, patients whose tumor cells expressed EpoR had a worse progression-free survival after the administration of epoetin beta compared with those assigned placebo, whereas epoetin beta did not impair the outcome as compared with placebo in patients whose tumor cells were negative for EpoR.

Although these studies reported increased cardiovascular and thromboembolic events in Epo-treated patients (a well characterized risk of Epo treatment), the bulk of increased deaths was attributable to accelerated cancer progression. By contrast ESAs, which include Epo, did not reduce the survival rate of patients with small-cell lung cancer. Epo may be considered as an endogenous stimulator of vessel growth during tumour progression through an autocrine and/or paracrine loop. The negative effect of Epo on tumour growth may be further aggravated by its angiogenic activity. Epo administration to patients with multiple myeloma or with myelodysplastic syndrome might promote an angiogenic response in their bone marrow and cause further malignant transformation, resulting in plasma cell leukaemia and acute monoblastic leukemia, respectively.