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Doxorubicin, Cardiac Risk Factors, and Cardiac Toxicity in Elderly Patients With Diffuse B-Cell Non-Hodgkin's Lymphoma

Dawn L. Hershman, Russell B. McBride, Andrew Eisenberger, Wei Yann Tsai, Victor R. Grann, Judith S. Jacobson

From the Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, and the Departments of Epidemiology and Biostatistics, Mailman School of Public Health, Columbia University; and New York Presbyterian Hospital, New York, NY

Corresponding author: 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

Purpose Anthracycline-based chemotherapy, which improves survival for patients with non-Hodgkin's lymphoma, is often withheld from elderly patients because of its cardiotoxicity. We studied the cardiac effects of doxorubicin in a population-based sample of older patients with diffuse large B-cell lymphoma (DLBCL).

Patients and Methods Among patients age 65 years diagnosed with DLBCL from 1991 to 2002 in the Surveillance, Epidemiology, and End Results–Medicare database, we developed logistic regression models of the associations of doxorubicin with demographic, clinical, and cardiac variables. We then developed Cox proportional hazards models of the association between doxorubicin and subsequent congestive heart failure (CHF), taking predictors of CHF into account.

Results Of 9,438 patients with DLBCL, 3,164 (42%) received doxorubicin-based chemotherapy. Any doxorubicin use was associated with a 29% increase in risk of CHF (95% CI, 1.02 to 1.62); CHF risk increased with number of doxorubicin claims, increasing age, prior heart disease, comorbidities, diabetes, and hypertension; hypertension intensified the effect of doxorubicin on risk of CHF (hazard ratio = 1.8; P < .01). In the 8 years after diagnosis, the adjusted CHF-free survival rate was 74% in doxorubicin-treated patients versus 79% in patients not treated with doxorubicin.

Conclusion Among patients receiving chemotherapy for DLBCL, those with prior heart disease were less likely than others to be treated with doxorubicin, and those who received doxorubicin were more likely than others to develop CHF. Various cardiac risk factors increased CHF risk, but only hypertension was synergistic with doxorubicin. Doxorubicin has dramatically improved survival of DLBCL patients; nonetheless, some subgroups may benefit from efforts to reduce doxorubicin-related CHF risk.

D.L.H. is the recipient of an American Society of Clinical Oncology Advanced Clinical Research Award. R.B.M. was supported in part by a R25 Award from the National Cancer Institute (CA94061) and a T32 Award (ULI RR024156) from the National Center for Research Resources of the National Institutes of Health.

This study used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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