Journal of the National Cancer Institute Advance Access published online on November 10, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp387
© The Author 2009. Published by Oxford University Press.
ARTICLE |
Patterns of Use and Risks Associated With Erythropoiesis-Stimulating Agents Among Medicare Patients With Cancer
Affiliations of authors: Department of Medicine and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons (DLH, AIN), and Department of Epidemiology and Department of Biostatistics, Mailman School of Public Health (DLH, DLB, RM, WYT, AIN), Columbia University and New York Presbyterian Hospital, New York, NY (JM); Greater Los Angeles VA Healthcare System, Los Angeles, CA (JM)
Correspondence to: Dawn L. Hershman, MD, MS, Columbia University Medical Center, 161 Fort Washington Ave, 10-1068, New York, NY 10032 (e-mail: dlh23{at}columbia.edu).
Background: Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist.
Methods: We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results–Medicare database; who were diagnosed with colon, non–small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided.
Results: Among 56 210 patients treated with chemotherapy from 1991 through 2002, 15 346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991–2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12 522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34 820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups.
Conclusion: Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.
| CONTEXT AND CAVEATS Prior knowledge Although erythropoiesis-stimulating agents have been approved to reduce the number of blood transfusions required during chemotherapy, increased risks of venous thromboembolism and mortality have been reported. Study design Patients who were aged 65 years or older; who were diagnosed with colon, non–small cell lung, or breast cancer or diffuse large B-cell lymphoma in 1991–2002; and who received chemotherapy were identified in the Surveillance, Epidemiology, and End Results–Medicare database. The association between erythropoiesis-stimulating agent use and venous thromboembolism and overall survival were analyzed. Contribution The proportion of patients receiving erythropoiesis-stimulating agents increased approximately 10-fold from 1991 through 2002. The rate of blood transfusion per year during 1991–2002 remained constant at 22%. More patients who received an erythropoiesis-stimulating agent than patients who did not developed venous thromboembolism. Overall survival was similar in both groups. Implications Further efforts are warranted to monitor the use and long-term toxicity of expensive oncology drugs, such as erythropoiesis-stimulating agents, to ensure that the benefits of any drug outweigh the risks in community practice. Limitations It is possible that venous thromboembolism would be diagnosed but not reflected in the billing claims used from the database and that not all treatments with erythropoiesis-stimulating agents or all transfusions were captured. Hemoglobin levels for individual patients were not available. From the Editors
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Manuscript received July 3, 2009; revised September 25, 2009; accepted September 28, 2009.