Patterns of use and risks associated with erythropoiesis-stimulating agents among Medicare patients with cancer.
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.


CONCLUSIONS
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.
Hershman
Dawn L
DL
Columbia University Medical Center, 161 Fort Washington Ave, 10-1068, New York, NY 10032, USA. dlh23@columbia.edu
Buono
Donna L
DL
Malin
Jennifer
J
McBride
Russell
R
Tsai
Wei Yann
WY
Neugut
Alfred I
AI
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy* / Q000628:therapy; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D015986:Confounding Factors, Epidemiologic; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008297:Male; D008498:Medical Record Linkage; D006278:Medicare; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012307:Risk Factors; D018426:SEER Program; D014481:United States / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000139:chemically induced
D000970:Antineoplastic Agents; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa