Congestive heart failure in patients treated with doxorubicin

Swain, Sandra M.; Whaley, Fredrick S.; Ewer, Michael S.

doi:10.1002/cncr.11407

Cited by 1,891 publications

(1,276 citation statements)

References 16 publications

Supporting

Mentioning

1,184

Contrasting

Unclassified

Order By: Relevance

“…5 Higher treatment-related mortality has also been reported in older patients using the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, 6,7 and several recent studies have shown that anthracycline-related cardiotoxicity is more frequent in this group of patients. 8,9 These findings have often led to arbitrary dose reductions or use of less-aggressive therapy, which may reduce the possibility of cure.…”

mentioning

confidence: 99%

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

Musolino

Boggiani

Panebianco

et al. 2010

Cancer

View full text Add to dashboard Cite

BACKGROUND: This study was designed to assess the activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab (DA-POCH-R) in elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma (DLBCL). METHODS: From April 2006 to November 2009, 23 patients, aged !70 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled. Only patients with left ventricular ejection fraction (LVEF) !50% were allowed. The DA-POCH-R regimen was administered every 3 weeks for a minimum of 6 and a maximum of 8 cycles. RESULTS: Median patient age was 77 years (range, 70-90 years); 83% of patients had Ann Arbor stage III to IV disease. Median LVEF at baseline was 62%. Four (17%) patients had a history of abnormal cardiovascular conditions. Twenty-one (91%) patients were evaluable for response. The overall response rate was 90%, with a complete response rate of 57%. The 3-year overall survival and event-free survival rates were 56% and 54%, respectively. Neutropenia (48%) was the most frequent grade 3 to 4 adverse event (AE); no grade 3 to 4 cardiac AEs were observed. CONCLUSIONS: DA-POCH-R was an active and safe combination therapy for patients aged !70 years with poor-prognostic untreated DLBCL. This regimen was a reasonable alternative for elderly patients who were not considered to tolerate standard R-CHOP treatment. Cancer 2011;117:964-73.

show abstract

mentioning

confidence: 99%

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

Musolino

Boggiani

Panebianco

et al. 2010

Cancer

View full text Add to dashboard Cite

show abstract

“…Despite its efficacy, the drug is associated therapeutically with a dilated cardiomyopathy (1), and more than a quarter of patients who receive DOX develop significant cardiac morbidity (2). DOX cardiotoxicity entails the generation of ROS by mitochondria -distinct on a molecular basis from its antineoplastic activity, which involves sequence-selective DNA intercalation and inhibition of topoisomerase II (3).…”

Section: Introductionmentioning

confidence: 99%

The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy

Suliman¹,

Carraway²,

Ali³

et al. 2007

J. Clin. Invest.

170

235

View full text Add to dashboard Cite

The clinical utility of anthracycline anticancer agents, especially doxorubicin, is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse heart fails to upregulate the nuclear program for mitochondrial biogenesis and its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive wall stress and fibrosis. Furthermore, we exploited recent evidence that mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial pathology was averted by periodic CO inhalation, which restored mitochondrial biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis-inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis.

show abstract

“…Because of the association of serious cardiotoxicities and leukemia with anthracyclines, 15 nonanthracyclinebased chemotherapeutic agents have been evaluated for their roles in the treatment of breast cancer. Taxanes have emerged as the most effective alternative to doxorubicin.…”

mentioning

confidence: 99%

Differential response of triple‐negative breast cancer to a docetaxel and carboplatin‐based neoadjuvant treatment

Chang¹,

Glaspy²,

Allison³

et al. 2010

Cancer

107

View full text Add to dashboard Cite

BACKGROUND:In this study, the authors evaluated whether a pathologic complete response (pCR) or a clinical complete response (cCR) to neoadjuvant treatment in patients with locally advanced breast cancer differed among the 3 subtypes of breast cancer: triple-negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and hormone receptor-positive/HER2-negative breast cancer. Whether a cCR or a pCR was correlated with fewer recurrences and better survival also was investigated. METHODS: Patients with stage II/III breast cancer received 4 cycles of neoadjuvant docetaxel and carboplatin (TC) every 3 weeks. Patients with HER2-positive tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone. Postoperatively, all patients received 4 cycles of TC, and all HER2-positive patients received a total of 52 weeks of trastuzumab. The recurrence-free survival (RFS) and overall survival (OS) rates at 2 years were reported. RESULTS: Seventy-four patients were enrolled, including 11 patients with TNBC, 30 patients with HER2-positive tumors, and 33 patients with hormone receptor-positive/HER2-negative tumor. The cCR rates were 45.4%, 50% and 40.6% in TNBC, HER2-positive, and hormone receptor-positive/HER2-negative groups, respectively. The pCR rate for the entire group was 26.8%, and patients with TNBC had the best response (54.6%) followed by patients with HER2-positive tumors (24.1%) and patients with hormone receptor-positive/HER2-negative tumors (19.4%; P ¼ .0126). The pCR rate for patients with HER2-positive tumors improved from 7% to 40% if trastuzumab was added (P ¼ .08). Infiltrating ductal cancer, TNBC, negative estrogen receptor and/or progesterone receptor status, tumor classification predicted a pCR (P .05). Multivariate analysis using a logistic regression test indicated that tumor type was an independent predictor. The RFS rate for patients who did versus patients who did not achieve a pCR was 93.8% versus 78.4% at 2 years, respectively, and 83.3% versus 58% at 3 years, respectively (P ¼ .1227); whereas, for patients who did versus patients who did not achieve a cCR, the RFS rate was 80.9% versus 83.9%, respectively, at 2 years and 65% versus 64.3%, respectively, at 3 years (P ¼ .999). CONCLUSIONS: The current results indicated that the TC combination is promising for the treatment of TNBC. The addition of trastuzumab to TC improved the pCR rate significantly in patients with HER2-positive breast cancer.

show abstract

Congestive heart failure in patients treated with doxorubicin

Cited by 1,891 publications

References 16 publications

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy

Differential response of triple‐negative breast cancer to a docetaxel and carboplatin‐based neoadjuvant treatment

Contact Info

Product

Resources

About