PURPOSE: The dose intensity of doxorubicin (DID) is important to the survival of diffuse large B cell lymphoma (DLBCL) patients. However, due to expected toxicities, most elderly patients cannot receive full doses of anthracyclines. The purpose of this study was to evaluate the effect of DID on the survival of elderly DLBCL patients (age > or = 70 years) in the rituximab era. MATERIALS AND METHODS: We analyzed 433 DLBCL patients who were treated with R-CHOP between December 2003 and October 2011 at the Seoul National University Hospital. Of these patients, 19.2% were aged > or = 70 years. We analyzed the survival outcomes according to DID. RESULTS: Significantly poorer overall survival (OS) was observed for patients aged > or = 70 years (2-year OS rate: 59.9% vs. 84.2%; p < 0.001). DID < or = 10 mg/m2/wk had a significant effect on the OS and progression-free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID < or = 10 mg/m2/wk vs. 62.6% in DID > 10 mg/m2/wk; p=0.031; 2-year PFS: 35.0% vs. 65.7%; p=0.036). The OS on each 1.7 mg/m2/wk doxorubicin increment above 10 mg/m2/wk in elderly patients was not significant among the groups (2-year OS rate: 75.0% in DID 10.0-11.7 mg/m2/wk vs. 66.7% in DID 15.0-16.7 mg/m2/wk; p=0.859). Treatment related mortality was not related to DID. CONCLUSION: DID can be reduced up to 10 mg/m2/wk in elderly DLBCL patients in the rituximab era. Maintenance of DID > 10 mg/m2/wk and judicious selection of elderly patients who are tolerant to DID is necessary.
Aged* ; Anthracyclines ; Disease-Free Survival ; Doxorubicin* ; Humans ; Lymphoma, B-Cell ; Mortality ; Seoul

Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline-induced cardiotoxicity and strategies for protecting the myocardium from anthracycline.
Anthracyclines ; Appointments and Schedules ; Breast Neoplasms ; Cardiotoxicity* ; Comorbidity ; Doxorubicin ; Drug Therapy ; Humans ; Leukemia ; Lymphoma ; Myocardium ; Sarcoma

PURPOSE: Anthracycline induced cardiotoxicity is well known and its pathology is characterized by localized myocardial cell necrosis and myocardial fibrosis. The variability in QT interval duration amongst the different leads of the standard 12-lead ECG(QT dispersion) is considered to reflect inhomogenous repolarization of the myocardium. The aim of this study was to assess the effects of anthracycline on cardiac electrophysiology, with special emphasis on dispersion of QT interval and its relation to cumulative doses. METHODS: Heart rate-corrected QT interval(QTc) and QT dispersion(QTd) were measured in standard 12-lead ECG in 34 cancer patients and compared with those of normal control. RESULTS: QTc was increased in cancer patients(462.2+/-36.0 msec vs 447.0+/-19.7 msec) but QTd was not different between the cancer patients and normal control as a whole(40.8+/-12.5 msec vs 36.6+/-9.2 msec). But in the 5-10 year age group, QTd was increased in cancer patients in comparison with that of age matched control(44.1+/-14.8 msec vs 34.0+/-9.7 msec). Also QTc in the 5-10 year age group, but not in the 11-15 year age group, was increased in cancer patients in comparison with that of age matched control(478.0+/-40.8 msec vs 446.5+/-20.9 msec). QTc and QTd were not different according to the cumulative doses of anthracycline in the cancer patients. Left ventricular systolic function was found normal in all cancer patients by echocardiographic examination. CONCLUSION: In the absence of a significant modification of echocardiographic parameters, increased inhomogeneity of ventricular repolarization could be an early marker of anthracycline cardiotoxicity. The changes of repolarization parameters were significant only in the younger age group and were not significant according to the cumulative doses. Anthracycline seemed to induce cardiotoxity from the small dose and more significantly in the younger heart.
Anthracyclines* ; Cardiac Electrophysiology ; Child* ; Drug Therapy* ; Echocardiography ; Electrocardiography ; Fibrosis ; Heart ; Humans ; Myocardium ; Necrosis ; Pathology

PURPOSE: The anthracyclines (AC) are widely used chemotherapeutic agents for pediatric cancers. However, the therapeutic use of these agents is limited by their cardiotoxicity. The aim of the present study was to investigate the usefulness of plasma B-type natriuretic peptide (BNP) levels as a marker for AC-induced cardiotoxicity compared to echocardiography in Korean children with cancer. METHODS: Fifty-five pediatric cancer patients who had received chemotherapy including AC were enrolled. The cumulative AC doses, clinical symptoms, and two echocardiography parameters, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF), were studied and compared with plasma BNP levels. RESULTS: In 55 patients, plasma BNP levels were measured 115 times and echocardiographies were performed 64 times. The median cumulative dose of AC was 325 mg/m2 (range 120-600; mean 345) and the median plasma BNP level was 10 pg/mL (range 5-950; mean 31). The cumulative AC doses correlated significantly with the plasma BNP levels (P=0.002). The plasma BNP levels correlated significantly with LVFS (P=0.018) and LVEF (P=0.025). Dilated cardiomyopathies were identified in three patients. LVFS and LVEF decreased and plasma BNP levels increased in a patient with acute dilated cardiomyopathy and in that with symptomatic chronic dilated cardiomyopathy. However, LVFS, LVEF and plasma BNP levels were normal in a patient with asymptomatic chronic dilated cardiomyopathy. CONCLUSION: The results of this study demonstrated that plasma BNP levels could be used as a marker for AC-induced cardiotoxicity; they showed good correlation with echocardiography findings in pediatric cancer patients. Plasma BNP levels may be used for the detection and management of AC-induced cardiotoxicity in Korean children with cancer.
Anthracyclines ; Cardiomyopathy, Dilated ; Child* ; Drug Therapy ; Echocardiography ; Humans ; Natriuretic Peptide, Brain* ; Plasma* ; Stroke Volume

BACKGROUND AND OBJECTIVES: Anthracyclines are effective drugs that are widely used in pediatric cancer treatment. Previous studies have demonstrated that exposure to low-dose anthracyclines (<300 mg/m2) induces a progressive decrease in cardiac function during long-term follow-up. The goal of this study was to assess left ventricular function using vector velocity imaging (VVI) in children undergoing low-dose anthracycline therapy. SUBJECTS AND METHODS: We examined 14 asymptomatic patients who had been treated with anthracyclines and had normal fractional shortening (FS) and ejection fraction (EF). In all of the patients, standard two-dimensional (2D) pulsed and tissue Doppler echocardiographic measurements were taken from an apical 4-chamber view. The peak myocardial velocity, peak strain rate (SR), peak strain, and displacement were obtained from VVI. Data were compared with 14 age-matched healthy controls. RESULTS: From the regional wall motion analysis using VVI in the left ventricle, the peak myocardial velocity and displacement of the lateral wall were increased significantly more than the septum, and there were no significant differences between the patients and the controls. Although systolic strain, and the systolic and diastolic SRs showed no significant differences between the septum and lateral wall in the controls, those of septum, in the patients, were decreased significantly more than those of lateral wall (p<0.05). In comparison with the controls, these changes in septal strain and SRs of patients were significant (p<0.05). CONCLUSION: Anthracycline therapy, even low-dose, can induce changes in regional wall function before global dysfunction. Also, the strain and SR obtained from VVI may be useful for early detection of these changes.
Anthracyclines ; Child ; Displacement (Psychology) ; Follow-Up Studies ; Heart Ventricles ; Humans ; Sprains and Strains ; Ventricular Function, Left

OBJECTIVETo evaluate the sensitivity of NT-pro-BNP in daunorubicin (DNR) induced myocardial damage by monitoring the level of NT-pro-BNP and myocardial enzymes (CK, CKMB) before and after DNR treatment in childhood acute leukemia (AL) and performing control study.

METHODSSixty-two cases (total 194 samples) which diagnosed as primary AL were enrolled and had received the conventional chemotherapy. According to the cumulative dose of DNR, they were divided into three groups: cumulative dose ≤ 60 mg/m(2) (group A); cumulative dose 60 - 120 mg/m(2) (group B); cumulative dose > 120 mg/m(2) (group C) and 15 cases with idarubicin (IDA) or mitoxantrone (MXR) as altervative to DNR (group D).

RESULTSThere was a significant difference (P = 0.000) in the level of NT-pro-BNP before and after DNR therapy, but did not in the myocardial enzymes activities (CK, P = 0.085 and CKMB, P = 0.076). The level of NT-pro-BNP appeared obviously elevated (P = 0.001) when DNR cumulative dose > 60 mg/m(2). While the level of CKMB did (P = 0.022) until DNR cumulative dose > 120 mg/m(2). In the 15 cases used IDA or MXR as alternative to DNR, the level of NT-pro-BNP fall from (239.9 ± 230.0) ng/L to (137.0 ± 131.9) ng/L (P = 0.024).

CONCLUSION(1) Compared with myocardial enzymes detection, NT-pro-BNP level can predict earlier DNR-induced cardiotoxicity. (2) Selection of the second or third generation anthracycline to treat AL can significantly reduce the cardiotoxicity in children.

PURPOSE: Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored. MATERIALS AND METHODS: Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectives were exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered. RESULTS: Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastro-intestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002). CONCLUSION: This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.
Anthracyclines ; Asthenia ; Breast Neoplasms* ; Breast* ; Humans ; Microtubules ; Multivariate Analysis ; Neutropenia ; Prospective Studies* ; Retrospective Studies ; Taxoids

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.
Anthracyclines/adverse effects* ; Cardiotoxicity/etiology* ; Drug Combinations ; Drugs, Chinese Herbal/adverse effects* ; Humans

Anthracyclines/adverse effects* ; Antibiotics, Antineoplastic ; Cardiotoxicity/diagnostic imaging* ; Echocardiography/methods* ; Humans ; Polyketides ; Technology

: ]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL). METHODS: The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups. RESULTS: There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770). CONCLUSION For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.
Anthracyclines ; Antineoplastic Combined Chemotherapy Protocols ; Humans ; Leukemia, Promyelocytic, Acute ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Tretinoin