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Venous thromboembolic events (VTEs) are frequent in cancer patients because of the effects of malignant disease, its treatment, and comorbidities. The higher risk for VTEs associated with the use of erythropoiesis-stimulating agents (ESAs) appears to be a class effect but may be particularly pronounced when these agents are used in patients who are not anemic at baseline and/or to achieve hemoglobin targets higher than those recommended in current labeling. Particular attention should be taken to assess the balance of risks and benefits in patients with a history of thromboembolism. If the goal of treatment of patients with chemotherapy-associated anemia is aimed to raise the hemoglobin level to 12 g/dl, and is confined to that, ESA-induced VTEs should rarely be a problem.

Learning Objectives After completing this course, the reader will be able to: Understand the etiology, symptoms, and impact (as reported by patients) of cancer- and chemotherapy-associated anemia. Recognize the clinical evidence supporting the efficacy of epoetin alfa in reducing transfusion requirements, increasing hemoglobin levels, and improving quality-of-life in anemic cancer patients receiving platinum- versus nonplatinum-based chemotherapy. Identify potential prognostic factors for responsiveness to epoetin alfa. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Background. Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based. Patients and Methods. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis. Results. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type. Conclusion. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

For 15 years, an overflowing literature has been published about MDR-1 gene expression in tumor cell lines and in cancerous tissues at various stages of disease and treatment (chemotherapy-naive, during treatment and at relapse). However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor responsible for the development of chemoresistance, is currently reconsidered. MDR-1 gene expression seems to be, at least in some instances, a hallmark of tumor cell aggressiveness and of chemoresistance rather than its cause, the mechanisms of which are probably far more complex. The failure of MDR reversal trials might result from the misunderstood or overvalued role of MDR expression in cancer cells rather than from a lack of control of pharmacological parameters. This review summarizes recent data and hypothesis about the expression of P-170 and its clinical significance in some important human tumor types, suggesting that it should rather be considered in the future as an adverse prognostic factor.

Learning Objectives After completing this course, the reader will be able to: Recognize the causes of anemia in cancer patients. Describe ways in which the action of erythropoietin is regulated. Explain the methods for treating anemia and indications for treatment. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com More than 30% of cancer patients experience anemia and its side effect, fatigue. Its causes can be numerous, but anemia is usually secondary to an imbalance of cytokines. Among these, tumor necrosis factor-alpha seems to be the major culprit, creating anemia by blunting the physiological effect of erythropoietin. Pharmacologically increasing the erythropoietin level corrects the anemia in about half the treated patients. Several studies have shown that quality of life is substantially improved through such therapy.

Safety concerns have arisen about the possibility of erythropoiesis-stimulating agents (ESAs) promoting tumor growth and increasing the incidence of venous thromboembolic events (VTEs). Because of the reported presence of erythropoietin receptors (EPORs) on tumor cells, it was questioned if ESAs had the potential for promoting tumor growth through stimulation of EPORs and tumor vessels and/or enhanced tumor oxygenation. Studies have shown that EPOR mRNA can be isolated from tumor cells, but the presence of EPOR protein has not yet been proven because of a lack of specific antibodies against EPORs. It is questionable whether EPORs on tumor cells are functional and there is no evidence that ESAs (within the approved indication in patients receiving chemotherapy) can stimulate EPORs on tumor cells in vivo. VTEs are frequent in cancer patients, resulting from the effects of malignant disease, cancer treatments, and comorbidities. VTEs are a leading cause of death in cancer patients. There are concerns about ESAs and a possible higher risk for VTEs and shorter survival in cancer patients. The higher risk for VTEs associated with ESAs appears to be a class effect, but the risk may be particularly pronounced when ESAs are used off label, as seen in clinical trials that targeted hemoglobin levels higher than those recommended by current ESA labeling and trials that enrolled patients who were not anemic at baseline. ESA treatment should be used within labeling confines.