Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma.
OBJECTIVE
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).


METHODS
Among patients age > or = 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.


CONCLUSIONS
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.
Hershman
Dawn L
DL
Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. dlh23@columbia.edu
McBride
Russell B
RB
Eisenberger
Andrew
A
Tsai
Wei Yann
WY
Grann
Victor R
VR
Jacobson
Judith S
JS
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D054715:Cardiotoxins; D016009:Chi-Square Distribution; D015897:Comorbidity; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D016015:Logistic Models; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D006278:Medicare; D016016:Proportional Hazards Models; D012307:Risk Factors; D018426:SEER Program; D015996:Survival Rate; D014481:United States
D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004317:Doxorubicin