Anthracyclines In Treatment Research Articles

Cardiovascular risk of anthracyclines in treatment of breast cancer and its strategy

Objective To evaluate the clinical cardiovascular reverse reactions of the patients with breast cancer who received chemotherapy with anthracyclines. Methods Two hundred and ninety-one cases of breast cancer who were treated with pirarubicin (40 mg/m2) + docetaxel (75 mg/m2) in Shanxi Provincial Cancer Hospital from January 2014 to December 2016 were collected. The changes of electrocardiogram (ECG), echocardiography and myocardial enzyme were recorded before and after chemotherapy. Results Before chemotherapy, there were 14 patients (4.8%) with ST-T segment changes before ECG, 6 patients (2.1%) with atrial extrasystole, 8 patients (2.7%) with ventricular extrasystole. After chemotherapy, cases with abnormal ECG were 62 (21.4%), 47 (16.2%) and 52 (17.9%) respectively. The difference between the two groups was statistically significant (χ 2 = 6.249, P < 0.005). The average left ventricular ejection fraction after chemotherapy was significantly lower than that before chemotherapy (0.72±0.10 vs. 0.81±0.18, t = 3.480, P < 0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST) and creatine kinase CK (CK-MB) were (68±20), (35±13) and (15.1±4.0) U/L after chemotherapy respectively, which were significantly higher than those before chemotherapy [(50±12), (28±12) and (7.9±2.6) U/L], the differences were statistically significant (t values were 9.721, 5.137 and 18.850 respectively, all P < 0.005). Conclusion The use of anthracyclines results in the increased risk of ECG abnormalities and myocardial damage in patients with breast cancer, and cardiac dynamic monitoring should be noted during chemotherapy. Key words: Breast neoplasms; Drug therapy; Anthracyclines; Pirarubicin; Cardiovascular reverse reactions

Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.

Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1/2 mutation carriers with early stage BC.

Long‐term survivor of relapsed stage IV malignant rhabdoid tumor of the kidney

The prognosis for metastatic malignant rhabdoid tumor (MRT) is poor, and metastatic (stage IV) MRT was resistant to conventional treatment, with less than 20% of cure rate. Moreover, there have been no reports of patients who have survived relapsed stage IV MRT. Here we report a long-term survivor of relapsed MRT with lung metastasis at diagnosis. He was diagnosed as MRT of the kidney at 5-month-old. After resection of the renal tumor, he was treated with ICE (ifosfamide, carboplatin, and etoposide), total abdominal irradiation 10.8 Gy and high-dose chemotherapy using thiotepa and melphalan. Six months after initial treatment, a relapse in the lung was detected, and he received chemotherapy including doxorubicin/pirarubicin for 78 weeks. He is alive at five years of follow up, without any evidence of disease. Our report suggests the important role of anthracycline in treatment of MRT.

Role of Anthracyclines in the Treatment of Early Breast Cancer

To review data relating to anthracyclines in the adjuvant treatment of early breast cancer. This is a report from a seminar in which the future of anthracyclines in the adjuvant treatment of breast cancer was considered. In particular, the question of whether anthracyclines should now be discarded and replaced by taxanes was addressed. Accumulating data from large randomized trials indicate that genetic markers may have a role in predicting sensitivity to cytotoxic drugs. However, no reliable, validated test is available for predicting sensitivity to anthracyclines in particular. Topoisomerase IIalpha amplification and/or deletion, especially in conjunction with human epidermal growth factor receptor-2 amplification, has been proposed to fulfill this role but more data are needed. Currently, only one published trial has shown that a taxane-based regimen may be superior to an anthracycline-based regimen, but several trials indicate that combinations including both anthracyclines and taxanes may be better still. Further studies aimed at optimizing anthracyclines and taxanes in combination, and integrating biologic agents, seem to be the way forward. There is no validated test that can determine whether anthracyclines can be of greater benefit than other agents for individual patients. Anthracyclines have been extensively tested in clinical trials spanning several decades; currently, there are insufficient data to recommend replacing them in the adjuvant treatment of breast cancer.

Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction

The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy. We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference. A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF. In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy.

Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction

Background: The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy. Aim: We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference. Methods and results: A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF. Conclusions: In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy.

114 Idarubicin and daunorubicin binding to DNA in sensitive and resistant leukemia K562 cells

ldarubicin (IDA) is a most active anthracycline in treatment of acute myelogenous leukemias including those resistant to daunorubicin (DAU). To study this phenomenon we have compared IDA and DAU intracellular accumulation and binding to DNA in sensitive (sens) and resistant (res) human leukemia K562 cells and verapamil (Ver) influence on these parameters. It was shown: (1) binding to DNA of IDA in sens and res cells is higher than that of DAU; (2) both drugs’ binding to DNA is about two times higher in sens than in res cells; (3) after Ver preincubation IDA (but not DAU) binding to DNA in res cells achieves about the same value as in sens cells. The results can explain the higher clinical efficacy of IDA than DAU in treatment of sens and res leukemias and allow supposition that IDA efficacy can be further elevated by its combination with Ver. Supported by UICC, International Soros Foundation and Russian Foundation of Basic Researches.