Use of erythropoietin in oncology

Anemia is a common complication observed in cancer patients. Its etiology is multifactorial and its severity depends on patient characteristics, type and stage of neoplasia, type of used chemotherapy. Erythropoietin can be effective by counteracting two of the main causes of anemia in cancer patients undergoing chemotherapy: 1. Myelosuppression induced by chemotherapy. Almost all cytotoxic drugs induce this effect. In this circumstance erythropoietin can be effective by accelerating the recovery of the erythroid compartment spared by chemotherapy. For this effect, higher than physiologically normal levels of erythropoietin are required. 2. Endogenous erythropoietin deficiency secondary to renal impairment. Renal impairment is primarily induced by cisplatin and leads to a deficient renal production of erythropoietin. In this case, erythropoietin administration can be considered as a hormone replacement therapy. Possible indications for the use of erythropoietin in cancer patients are the following: 1. Prevention of anemia; 2. Treatment of anemia induced by either high dose chemotherapy and bone marrow transplantation (BMT) or standard dose chemotherapy. The preventive use of erythropoietin is still under investigation. Two randomized studies reported the erythropoietin ability to prevent the anemia development. Further trials are required to identify subsets of patients in which the preventive use of the drug could be cost-effective. One of the causes of anemia after allogeneic BMT is the endogenous production of erythropoietin inappropriately low for the degree of anemia. On the contrary, after autologous BMT the erythropoietin response to anemia is appropriate. Phase III randomized studies showed the efficacy of erythropoietin in the treatment of anemia after allogeneic but not after autologous BMT. After standard dose chemotherapy, phase III randomized studies showed that erythropoietin is able to correct anemia in 60-80% of patients receiving platinum-based chemotherapy and in nearly 40% of patients receiving chemotherapy without platinum. The correction of anemia leads to a significant reduction in transfusion requirement. In solid tumors erythropoietin is commonly administered at the schedule of 150 U/Kg subcutaneously three times per week. Normal levels of current iron supply should be guaranteed by oral iron support during erythropoietin treatment. Because the response to erythropoietin occurs after a median time of 5 weeks, it is necessary to start erythropoietin therapy at an hemoglobin level higher than that triggering transfusion. Various parameters, at baseline or after 2-4 weeks of erythropoietin therapy, have been evaluated as predictors of response. However, other parameters should be studied to identify stronger predictors. Conclusions. Erythropoietin treatment is recommended after allogeneic BMT. Erythropoietin is effective in 60-80% of anemic patients receiving platinum-containing chemotherapy and in approximately 40% of patients receiving chemotherapy without platinum. The preventive use of erythropoietin is still under investigation. Further studies should identify subsets of patients and types of chemotherapy in which the prevention of anemia could be cost/effective.