Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse b-cell non-Hodgkin's lymphoma

Abstract

9050 Background: Anthracyclines are known to cause acute and chronic cardiotoxicity. In a population-based sample of elderly patients with diffuse large B-cell lymphoma (DLBCL), we studied the cardiac effects of doxorubicin (DOX)-containing regimens and of pre-existing diabetes (DM), hypertension (HTN), and heart disease (HD). Methods: Patients aged =65 years diagnosed with DLBCL 1/1/1992–12/31/2000 in the SEER/Medicare database were grouped by treatment: no chemotherapy, doxorubicin-based chemotherapy, or other chemotherapy. We developed multivariable logistic regression models of the associations of DOX-based chemotherapy with demographic and clinical variables and pre-diagnosis DM, HTN, and HD. We then developed Cox proportional hazards regression models of the association between treatment and subsequent congestive heart failure (CHF) taking the predictors of treatment into account. Results: Of 6,413 patients with DLBCL, 2,536 (39%) received doxorubicin-based chemotherapy. DOX use was associated with later year of diagnosis, female gender, younger age, and being married. Black race (HR 0.50, 95% CI 0.33–0.75), comorbidities, preexisting CHF, HD, and DM (HR 0.73, 95% CI 0.62–0.86) were associated with decreased DOX use. The post-treatment HR for CHF following DOX treatment vs. no chemotherapy was 1.39 (95% CI 1.15–1.67); CHF risk increased with duration of DOX use. It was also associated with increasing age, comorbidities, black race, DM, HTN, and HD. There was a significant interaction between race and DOX (P=0.01); For black patients treated with DOX the HR for CHF was 3.4, as compared to a HR of 1.3 for white patients. Conclusions: Among patients with DLBCL, black race, CRFs and pre-existing HD are all associated with both a reduced likelihood of receiving anthracyclines, and an increased risk of CHF. We have previously found a powerful effect of DOX on survival in this patient population; thus, for most patients, the benefits of treatment would appear to outweigh the risks of cardiac toxicity. However, as the number of long-term survivors grows, the need for research on the side effects of treatment, on host factors that may increase the risk of adverse effects, and on ways to minimize such risks will also grow. No significant financial relationships to disclose.