scholarly journals Early Evidence of Cardiotoxicity and Tumor Response in Patients with Sarcomas after High Cumulative Dose Doxorubicin Given as a Continuous Infusion

Sarcoma ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Raymundo A. Quintana ◽  
Jose Banchs ◽  
Ridhi Gupta ◽  
Heather Y. Lin ◽  
Sean D. Raj ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Cumulative Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Disease Group ◽  
Ventricular Ejection Fraction ◽  
Early Evidence ◽  
High Cumulative Dose ◽  
Dose Dependent

Background. Despite the dose-dependent response rate of sarcomas to doxorubicin, clinicians limit its cumulative dose due to cardiotoxicity. This study evaluates early evidence of cardiotoxicity in patients treated with high-dose doxorubicin given as a continuous infusion. Methods. Data was collected on patients who received 90 mg/m2 doxorubicin as a continuous infusion and 10 gm/m2 ifosfamide for up to 6 cycles as part of a phase II study. Cardiotoxicity was assessed with serial echocardiograms or multigated acquisition scans and serum brain natriuretic peptide and troponin levels. Tumor responses were determined by serial radiographic imaging per RECIST. Result. Out of the 48 patients enrolled, no patient developed heart failure symptoms; however, 4 out of the 38 (10%) patients with serial left ventricular ejection fraction assessments developed subclinical cardiotoxicity (asymptomatic drop in LVEF ≥ 10%). Twenty-three patients received all six 72-hour cycles of doxorubicin with a mean cumulative dose of 540 mg/m2. Among these patients, 4% (n=1) developed subclinical cardiotoxicity. In the advanced disease group (n=39), patients with a complete or partial response received a higher mean cumulative dose than those with stable disease (p<0.033). Conclusions. Doxorubicin cardiotoxicity can be limited by administering doxorubicin as a continuous infusion, allowing higher cumulative dosing to maximize efficacy.

Prevalence of Major Cardiac Events of Anthracycline-Induced Cardiotoxicity in Southwestern Iran: Different Response Patterns to Cumulative Dose

2020 ◽  
Vol 15 (1) ◽  
pp. 78-84
Author(s):  
Mahsa Behrouzian ◽  
Babak Najibi ◽  
Sabahat Haghi ◽  
Chehreh Mahdavi ◽  
Kaveh Jaseb ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cumulative Dose ◽  
Chemotherapeutic Agents ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Significant Difference ◽  
High Cumulative Dose ◽  
And Control

Background: Anthracyclines are widely used chemotherapeutic agents in several cancers. Since its use, survival improved significantly among cancer patients and has been reported to be up to 80%. However, anthracyclines possess several cardiac, renal and hematological toxicities which limit their use in practice. Cardiotoxicity is still the most important and dose-limiting side effect of anthracycline treatment. Here we aimed to investigate the frequency of anthracyclineinduced cardiomyopathy in pediatric malignancies in Khuzestan Province, Iran. Methods: A total of 112 patients were enrolled in the present study. Patients were allocated to the case or control group based on receiving anthracycline. Echocardiographic examinations were performed by a cardiologist. Electrocardiograms were also recorded. Results: We showed that cancer patients who underwent anthracycline treatment showed cardiomyopathy as defined by lower LVEF (Left Ventricular Ejection Fraction) among patients (p = 0.041). Abnormal LVEF was reported with a frequency of about 9.5% in patients (p = 0.026). However, LVFS (Left Ventricular Fraction Shortening), QRS voltage and QT interval did not differ significantly between treatment and control groups. Our data analysis revealed that this difference is mainly related to high cumulative dose since high cumulative dose of anthracycline (>300 mg/m2) leads to lower LVEF and LVFS and higher QRS voltage in comparison with lower cumulative dose (<300 mg/m2) and control group; but there was no significant difference between low dose and control group. Different age groups and type of malignancy including hematological and solid tumors did not show any significant differences for echocardiographic and electrocardiograms parameters. Conclusion: In our study, lower LVEF among patients who received anthracyclines were mainly related to a high cumulative dose of anthracyclines, which emphasizes the effect of cumulative dose for cardiotoxic effects. Larger studies are needed to investigate possible other risk factors for cardiotoxicity.

scholarly journals Antibody-mediated rejection with detection of de novo donor-specific anti-human leucocyte antigen Class II antibodies 3 years after heart transplantation: a case report

2020 ◽  
Vol 4 (1) ◽  
pp. 1-4
Author(s):  
Bernd Ludwig ◽  
Johanna Schneider ◽  
Daniela Föll ◽  
Qian Zhou
Keyword(s):  
Heart Transplantation ◽  
De Novo ◽  
Survival Rates ◽  
Graft Function ◽  
Left Ventricular ◽  
Cardiac Allograft ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Ventricular Ejection Fraction ◽  
Antibody Mediated Rejection

Abstract Background Antibody-mediated rejection (AMR) in cardiac transplantation may manifest early within the first weeks after transplantation but also late after months to years following transplantation resulting in mild heart failure to cardiogenic shock. While patients with early cardiac AMR are less affected and seem to have survival rates comparable to transplant recipients without AMR, late cardiac AMR is frequently associated with graft dysfunction, fulminant forms of cardiac allograft vasculopathy, and a high mortality rate. Nevertheless, AMR of cardiac allografts remains difficult to diagnose and to treat. Case summary We report the case of a 47-year-old male patient with late AMR of the cardiac allograft 3 years after heart transplantation. Antibody-mediated rejection was confirmed by endomyocardial biopsy and the presence of donor-specific antibodies (DSA). The patient was treated with high dose of prednisolone, plasmapheresis, intravenous Gamma Globulin, rituximab, immunoadsorption, and bortezomib. Under this treatment regimen left ventricular ejection fraction and pro B-type natriuretic peptide recovered, and the patient improved to New York Heart Association Class I. Currently, 3 years after the diagnosis of cardiac AMR, graft function continues to be nearly normal, and there is no evidence for transplant vasculopathy. Discussion This case illustrates that AMR can occur at any time after transplantation. Although graft function fully recovered after treatment in our patient, the level of DSA remained high, suggesting that DSA may not be a reliable parameter to determine the intensity and duration of the therapy.

scholarly journals Transplantation of Endothelial Progenitor Cells in the Treatment of Coronary Artery Microembolism in Rats

2020 ◽  
Vol 29 ◽  
pp. 096368972091268
Author(s):  
Yajun Xue ◽  
Boda Zhou ◽  
Jian Wu ◽  
Guobin Miao ◽  
Kun Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Low Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

Neoadjuvant chemotherapy (NACT) with prolonged high-dose (HD) doxorubicin (A) and cyclophosphamide (C) with G-CSF support in locally advanced breast cancer (LABC): Long-term follow-up data

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11090-11090
Author(s):  
S. Altintas ◽  
M. T. Huizing ◽  
I. Spoormans ◽  
J. Van den Brande ◽  
P. Wilmes ◽  
...  
Keyword(s):  
Residual Disease ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Axillary Lymph ◽  
Study Objective ◽  
Ventricular Ejection Fraction

11090 Background: NACT improves survival in LABC. The optimal regimen, dose and duration is still under study Objective: To determine the efficacy and safety of prolonged preoperative HD-AC plus G-CSF. Methods: LABC patients (pts) were treated with AC for 6 cycles (Cy): Cy 1: A 90 mg/m2, C 1000 mg/m2; Cy 2–3: A 82.5 mg/m2, C 875 mg/m2; Cy 4–6: A 75mg/m2, C 750 mg/m2) with prophylactic (peg)filgastrim q3wks. In case of cardiotoxicity or poor tumor response (TR) pts switched to Docetaxel (D) 100mg/m2 q3wks. Within 5 weeks after NACT, pts underwent mastectomy with axillary lymph node dissection followed by radiotherapy. In case of positive estrogen (ER) or progesteron receptor (PgR), hormonal treatment was given for 5 yrs. Toxicity was scored weekly (NCI-CTC 2), response every 3 wks (WHO). Kaplan-Meier analysis was performed to calculate disease free survival (DFS) and overall survival (OS). Results: Between 8/1997 and 10/2003 21 pts (median age 55 years, range 22–74) were enrolled. One pt had stage IIB, 6 stage IIIA, 14 stage IIIB disease (10 T4d). 10 tumors were ER+, 5 PgR+, none overexpressed Her-2/Neu. A total of 130 NACT Cy was given. 15 pts completed all 6 AC Cy, 6 switched to D because of a decrease in left ventricular ejection fraction (LVEF? >10%, n=2) or insufficient TR (n=4). Dose reduction of AC was needed in 1 pt (last Cy), dose delays in 4 pts. Nausea and vomiting were generally mild; grade 4 anorexia occured in one pt. Grade 4 leucopenia and neutropenia in 14 and 18 pts, respectively. Neutropenic fever requiring hospitalization occurred in 5 pts, thrombocytopenia grade 4 in 7 pts and grade 3 anemia in 3 pts. Two pts developed cardiomyopathy (9.5%) < 2 years after NACT. The overall TR rate (PR and CR) was 81%, clinical CR rate 14%, pathologic CR rate 10% and 14% had minimal residual disease. Three pts showed SD and only 1 pt had PD. The median follow up of all pts was 51 months (range 9–110), 5 yrs DFS 47%, OS 56%. 5 yrs DFS and OS for pT4d pts was 50% and 56%, respectively. Conclusions: NACT with HD-AC plus G-CSF for 6 Cy in this poor risk population is active and further supports the use of prolonged preoperative CT. The routine use of D after a restricted number of AC Cy may further improve results and decrease (cardio)toxicity. No significant financial relationships to disclose.

Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin (PLD): Use of left ventricular ejection fraction (EF).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14016-e14016
Author(s):  
Keith M. Skubitz ◽  
Anne Hudson Blaes ◽  
Suma Konety ◽  
Gary S. Francis
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cumulative Dose ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Retrospective Chart Review ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Bolus Administration ◽  
Ventricular Ejection Fraction

e14016 Background: The use of doxorubicin (D) is limited by cardiotoxicity. Cumulative dose is an important risk factor for D-induced heart failure (D-HF). Retrospective studies found a ~7.5% incidence of clinical HF at a cumulative dose of 550 mg/m2, and prospective trials have found even higher rates. The administration of D by continuous intravenous infusion (CIVI) has less cardiotoxicity than when given by bolus administration. Pegylated-liposomal doxorubicin (PLD) has a longer half-life in blood, and may have lower cardiotoxicity. Limiting D use based on ejection fraction (EF) is commonly performed. Despite the wide use of EF to monitor D-HF, evidence for its utility to predict D-HF is limited, and monitoring adds cost. There is even less information regarding large cumulative doses of PLD and its effect on D-HF and EF. We examined the incidence of D-HF in patients who received a large cumulative dose of D as PLD, and its relation to EF and HF. Methods: A retrospective chart review of patients who received a large cumulative dose of PLD, sometimes following previous free D, was performed. Results: Definite clinical D-HF was not observed in 53 patients who received a cumulative D dose (free + PLD) of > 450 mg/m2, 46 of whom received > 500 mg/m2, 26 > 700 mg/m2, 14 > 1000 mg/m2, and 5 > 1400 mg/m2. The EF varied greatly over time in some patients in the absence of symptoms or signs of HF and was not a reliable predictor of the development of heart failure. Conclusions: The findings provide further evidence for the low risk of D-HF with PLD. Although this study is subject to the usual limits of a retrospective study, the doses received and long-term follow-up are noteworthy. While the determination of EF is commonly used to monitor D cardiotoxicity, it has many limitations. Serial monitoring of EF during treatment may not be helpful, at least in the case of PLD and CIVI-D in adults. Indeed, given the lack of prognostic clarity regarding modest EF changes, regular measurement of EF may sometimes inappropriately limit patient access to this useful drug. These findings may not apply to children or other liposomal formulations, such as non-pegylated formulations.

scholarly journals Prevalence of Anthracycline Induced Cardiomyopathy amongst Cancer Patients Treated at Tertiary Teaching and Refferal Hospital in Nairobi Kenya

2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Tonio C.N ◽  
Ogola E.N ◽  
Abinya N.A ◽  
Karari E M ◽  
Gitura B ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cumulative Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
National Hospital ◽  
Ventricular Ejection Fraction ◽  
Ground Floor ◽  
Kenyatta National Hospital ◽  
Tertiary Teaching ◽  
The Mean

Background: Cardiovascular complication is a major consequence of cancer treatment. Anthracycline induced cardiomyopathy is a known cause of long term morbidity and mortality among cancer survivors. The burden of this complication is unknown in our setting Objective: This study aimed to determine the prevalence of cardiomyopathy in ambulatory patients treated with anthracycline (Ac) containing chemotherapy at Kenyatta National Hospital (KNH) as measured by two dimensional (2D) echocardiography (ECHO). Study design: A hospital based inpatient/outpatient cross sectional, descriptive study. Study setting: This study was carried out in various outpatient clinics and oncology wards in Kenyatta National Hospital. These included the adult hematooncology clinic 23, Ground floor C (GF-C), Ward 8C and Ground floor D (GF-D) Subjects: The study population included patients who have been exposed to Ac. The minimum Ac dose was 200mg/m2. A total of 129 patients with various types of cancers were sampled consecutively over a period of 3 months. Eligible patients underwent a 2D ECHO and left ventricular ejection fraction (LVEF) was assessed. Results: Patients between the ages of 15 and 75 participated in the study, the mean age was 45.6 years, with the female to male ratio of 4.3:1. Majority of the patients had breast cancer (67.4%) and the treatment regimen in over 65% of them was doxorubicin and cyclophospomide (AC). The mean cumulative dose was 236mg/m2. All patients recruited had received a cumulative dose of between 200 - 450mg/m2. Most of the patients (63%) had completed Ac within one year of their cardiac evaluation. Only 14.0 % of the patients had a pretreatment ECHO. The overall prevalence of LV systolic dysfunction detected by echocardiography was 3.1% (95% CI 0.9– 7.8). The study was not powered to make associations with age, sex and cumulative dose and presence of cardiomyopathy. Conclusions: The study demonstrates a prevalence of 3.1% cardiomyopathy among cancer patients treated with anthracyclines. This figure is comparable to similar studies done. The prevalence described in most studies ranges from between 1% to 20.5%.Anthar

scholarly journals Tianxiangdan Improves Coronary Microvascular Dysfunction in Rats by Inhibiting Microvascular Inflammation via Nrf2 Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guligena Sawuer ◽  
Xue-Kuan Ma ◽  
Ya-Jie Zhang ◽  
Xuan-Ming Zhang ◽  
Zulihumaer Ainiwaer ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coronary Microvascular Dysfunction ◽  
Heme Oxygenase 1 ◽  
High Dose ◽  
Related Factor ◽  
Nuclear Factor ◽  
Necrosis Factor Alpha ◽  
Ventricular Ejection Fraction ◽  
Tnf Α

Background. Tianxiangdan (TXD) is used in traditional Chinese medicine because of its therapeutic and preventive effects in the treatment of coronary heart disease. However, the underlying mechanism of TXD in coronary microvascular disease (CMD) remains unclear. Methods. A rat model of CMD was developed to study the mechanism of TXD activity. Sodium laurate was injected into the left ventricle of Sprague–Dawley rats to induce CMD. The rats were divided into six groups: a sham-operated (sham) group, an untreated CMD group, a low-dose TXD group (0.81 g·kg−1·d−1), a mid-dose TXD (TXD-M) group (1.62 g·kg−1·d−1), a high-dose TXD (TXD-H) group (3.24 g·kg−1·d−1), and a nicorandil (NCR) group (1.35 mg·kg−1·d−1). The effect of TXD on rats with CMD was observed after four weeks, and the mechanism of TXD in lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMECs) was explored through treatment with 50 μg/mL TXD. Results. Compared with the rats in the untreated CMD group, rats in the TXD-M and TXD-H groups showed higher left ventricular ejection fraction values, improved pathological structures, decreased expressions of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor-κB inhibitor α (IκBα) and phosphorylated p65, and increased expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 ( P < 0.05 ). These effects were more pronounced in the TXD-H group than in the TXD-M group. In vitro experiments showed that TXD treatment increased the viability of LPS-induced CMECs and decreased the expression of IL-1β, TNF-α, phosphorylated IκBα, and phosphorylated p65 ( P < 0.05 ). However, the effects of TXD on CMECs were markedly reversed upon treatment with ML385 (Nrf2 inhibitor). Conclusion. The results showed that TXD exerts a protective effect on rats with CMD and related inflammatory injuries, and its anti-inflammatory mechanism is related to the activation of Nrf2 signalling.

scholarly journals Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ayaka Ishihara ◽  
Shuji Hatakeyama ◽  
Jun Suzuki ◽  
Yusuke Amano ◽  
Teppei Sasahara ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Cumulative Dose ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Pegylated Liposomal Doxorubicin ◽  
Kaposi Sarcoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Background Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. Case presentation A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient’s left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. Conclusions This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.

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