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Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required. [Display omitted] • Two-thirds of the Japanese patients experienced cancer therapy-related cardiac dysfunction (CTRCD). • CTRCD was frequently observed at 3 or 6 months post-anthracycline-based chemotherapy. • All patients with CTRCD were diagnosed with mild asymptomatic CTRCD. [ABSTRACT FROM AUTHOR]

Left ventricular dysfunction in dogs after the administration of doxorubicin (DOX) has been extensively examined. However, the effects of DOX on right ventricular (RV) function remain unknown. Therefore, the present study investigated whether the chemotherapy treatment with DOX decreases RV function. Twelve dogs (five with multicentric lymphoma, four with hemangiosarcoma, two with thyroid cancer, and one with lung adenocarcinoma) that received at least two doses of DOX were prospectively enrolled. Echocardiography and the measurement of troponin I were performed prior to each administration of DOX and approximately one month after the last administration. Right ventricular function was assessed by the RV fractional area change and RV Tei index. Two (n=4), three (n=3), four (n=3), and five (n=2) doses of DOX were administered. While no significant differences were observed in the RV fractional area change, the RV Tei index was significantly impaired after two doses of DOX. Troponin I level significantly increased after four doses. Cumulative doses of DOX correlated with the RV Tei index (r=0.77, P<0.001). The present results demonstrated that the chemotherapy treatment with DOX decreased RV function in a dose-dependent manner in dogs. [ABSTRACT FROM AUTHOR]

Anthracycline chemotherapy-related cardiac dysfunction is believed to be refractory to conventional pharmacological therapy and is associated with a poor prognosis. Increased heart rate (HR) is a known marker of cardiovascular outcomes for various categories of heart failure (HF). However, little interest has been expressed regarding increased HR after anthracycline chemotherapy. Aim of this study was to investigate the effect of increased HR soon after completion of anthracycline chemotherapy on subsequent left ventricular (LV) ejection fraction (LVEF) in cancer patients. We studied 172 patients with breast cancer and malignant lymphoma with preserved LVEF (≥ 50 %) and sinus rhythm treated with anthracyclines. Electrocardiography was performed before and soon after completion of anthracycline chemotherapy (2.3 months), and echocardiography before and late after completion of anthracycline chemotherapy (10.5 months). HR significantly increased from 74.2 ± 14.2 bpm to 75.9 ± 13.2 bpm (P = 0.05) soon after completion of anthracycline chemotherapy, while LVEF subsequently significantly decreased from 65.3 ± 5.5 % to 62.4 ± 6.1 % (P < 0.01) late after completion of anthracycline chemotherapy. Patients whose HR increased ≥10 bpm subsequently showed a significantly greater decrease in LVEF than those whose HR increased <10 bpm [−4.9 % (−32.7 % - 10.8 %) vs. -2.2 % (−21.2 % - 12.9 %), p = 0.04]. Multivariable logistic regression analysis showed that an increase in HR soon after completion of anthracycline chemotherapy was independently associated with a subsequent decrease in LVEF (odds ratio: 1.022, 95 % confidential interval; 1.008–1.037, P = 0.002). Our findings may have a novel effect on the management of cancer patients scheduled for anthracycline chemotherapy. [Display omitted] • Heart rate (HR) increased soon after completion of anthracycline chemotherapy. • Left ventricular ejection fraction (LVEF) subsequently decreased late after completion of anthracycline chemotherapy. • Patients whose HR increased ≥10 bpm showed a greater decrease in LVEF. • Increased HR after anthracycline was associated with subsequent decrease in LVEF. [ABSTRACT FROM AUTHOR]

• The effect of sex on chemotherapy-associated heart failure has not been clearly established. • In this retrospective cohort study, female sex was not associated with heart failure after anthracycline treatment in multivariable analyses, including in a Cox proportional hazards model and in a competing risk model accounting for all-cause death. • Age, coronary artery disease and hematopoietic stem cell transplant were associated with an increased risk of incident heart failure within 5 years after anthracycline treatment in a multivariable Cox proportional hazards model. • Age and body mass index were associated with an increased risk of incident heart failure within 5 years after anthracycline treatment in a multivariable competing risk model. Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines. This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models. Over a median (IQR) follow-up of 1.02 (0.30–3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53–1.43; P = 0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39–2.25; P = 0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model. In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines. Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: Long-term cardiovascular complications are common among pediatric cancer survivors, and anthracycline-induced hypertension has become an essential reason for concern. Compared to non-cancer controls, survivors have a higher prevalence of hypertension, and as they age, their incidence rises, offering significant dangers to cardiovascular health. Main body: Research demonstrates that exposure to anthracyclines is a major factor in the development of hypertension in children who have survived cancer. Research emphasizes the frequency and risk factors of anthracycline-induced hypertension, highlighting the significance of routine measurement and management of blood pressure. Furthermore, cardiovascular toxicities, such as hypertension, after anthracycline-based therapy are a crucial be concerned, especially for young adults and adolescents. Childhood cancer survivors deal with a variety of cardiovascular diseases, such as coronary artery disease and cardiomyopathy, which are made worse by high blood pressure. In order to prevent long-term complications, it is essential to screen for and monitor for anthracycline-induced hypertension. Echocardiography and cardiac biomarkers serve as essential tools for early detection and treatment. In order to lower cardiovascular risks in pediatric cancer survivors, comprehensive management strategies must include lifestyle and medication interventions in addition to survivor-centered care programs. Short conclusion: Proactive screening, monitoring, and management measures are necessary for juvenile cancer survivors due to the substantial issue of anthracycline-induced hypertension in their long-term care. To properly include these strategies into survivor-ship programs, oncologists, cardiologists, and primary care physicians need to collaborate together. The quality of life for pediatric cancer survivors can be enhanced by reducing the cardiovascular risks linked to anthracycline therapy and promoting survivor-centered care and research. [ABSTRACT FROM AUTHOR]

It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12‑lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170–1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ± 27 ms vs. 411 ± 37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ± 24 ms vs. 395 ± 25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ± 53 ms vs. 211 ± 28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ± 19 ms vs. 225 ± 23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = −0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection. [Display omitted] • The prolongation of corrected activation recovery interval (ARIc) after chemotherapy was observed only in the CTRCD group • ARIc prolongation was associated with decreased left ventricular ejection fraction • The cut-off point of ARIc prolongation for the development of CTRCD is 18 ms (area under the curve 0.76) [ABSTRACT FROM AUTHOR]

BACKGROUND: Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. METHODS: In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. RESULTS: Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/ m², and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/ gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). CONCLUSIONS: Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. [ABSTRACT FROM AUTHOR]

Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the global burden of cardiovascular disease. CTRCD causes two crucial issues: first, premature treatment interruption or discontinuation of chemotherapy; second, the development of congestive heart failure during and after cancer treatment. Thus, early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. This review covers representative anticancer drugs, including anthracyclines, human epidermal growth factor 2 inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. We focus on the molecular mechanisms of CTRCD and various approaches to diagnosis, prevention, monitoring, and treatment. [Display omitted] • CTRCD significantly contributes to the global burden of cardiovascular disease. • Comprehensive cardiac monitoring may be useful during and after cardiotoxic chemotherapy. • Echocardiography and cardiac biomarkers play pivotal roles to detect CTRCD. • Early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. • Close collaboration between oncologists and cardiologists is becoming more and more important. [ABSTRACT FROM AUTHOR]

Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P < 0.0001) (P < 0.01), creatine kinase isoenzyme (SMD = −3.49; 95 % CI, −5.24 to −1.74; P < 0.0001), Prolonged QT interval (RR = 0.46; 95 % CI, 0.28 to 0.75; P = 0.0018), Low QRS Voltage (RR = 0.44; 95 % CI, 0.27 to 0.71; P = 0.0007), sinus tachycardia (RR = 0.41; 95 % CI, 0.28 to 0.60; P < 0.0001), atrial premature beats (RR = 0.55; 95 % CI, 0.35 to 0.87; P = 0.01), Premature Ventricular Contractions (RR = 0.39; 95 % CI, 0.26 to 0.59; P < 0.0001) and creatine kinase (SMD = −1.43; 95 % CI, −2.57 to −0.29; P < 0.0001) in patients with anthracycline-induced cardiotoxicity. advantage, which was supported by sensitivity analyses, but not in improving left ventricular ejection fraction (MD = 16.01; 95 % CI, −3.10 to 35.12; P = 0.10) and atrioventricular block (RR = 0.49; 95 % CI, 0.24 to 1.03; P = 0.06). The literature included in the study did not refer to data regarding the safety aspects of Shenmai injection, so we do not yet know the safety of Shenmai injection. The results of subgroup analyses suggested that heterogeneity was not related to the administered dose and chemotherapy regimen. The publication bias test showed no publication bias. The quality of evidence for the results ranged from "very low" to "moderate." This study suggests that Shenmai injection is effective in treating anthracycline-induced cardiotoxicity and is a potential treatment for anthracycline-induced cardiotoxicity. However, due to the poor methodological quality of the included RCTs, we recommend rigorous, high-quality, large-sample trials to confirm our findings. • The present study represents the inaugural evaluation of the effectiveness and safety of Shenmai injection therapy in the management of anthracycline-induced cardiotoxicity. Methodological robustness was ensured through assessment with AMSTAR 2, demonstrating adherence to high standards. Furthermore, the provision of thorough supplementary materials facilitates reproducibility and scrutiny of the research. Additionally, the incorporation of high-quality, sizable randomized controlled trials enhances the credibility of the findings, offering valuable insights for clinical decision-making and supplementation of extant international guidelines on cardiac toxicity. [ABSTRACT FROM AUTHOR]

P‐glycoprotein (Pgp) detoxifies cells by exporting hundreds of chemically dissimilar hydrophobic and amphipathic compounds and is implicated in multidrug resistance (MDR) in the treatment of cancers. Photoaffinity labeling of plasma membrane vesicles of MDR CHO B30 cells with the anthracycline [125I]‐iodomycin, subsequent sequential cleavage with BNPS‐skatol and endoproteinase Lys‐C, and the Edman sequencing of the purified photoaffinity‐labeled peptide identified the lysine residue at position 268 in the hamster Pgp primary sequence as the major photobinding site of iodomycin in CHO B30 cells. Lysine 268 is located adjacent to the cytosolic terminus of transmembrane 5. According to thermodynamic and kinetic analyses, this location should present the equilibrium binding site of ATP‐free Pgp for daunomycin and iodomycin in B30 cells. [ABSTRACT FROM AUTHOR]

CHILDREN with cancer and survivors of childhood cancer have an increased risk of cardiovascular disease, and this risk in the perioperative period must be understood. During diagnosis and treatment of pediatric cancer, multiple acute cardiovascular morbidities are possible, including anterior mediastinal mass, tamponade, hypertension, cardiomyopathy,and heart failure. Childhood cancer survivors reaching late childhood and adulthood experience substantially increased rates of cardiomyopathy, heart failure, valvular disease, pericardiac disease, ischemia, and arrhythmias. Despite considerable advances in the understanding and therapeutic options of pediatric malignancies, cardiac disease remains the most common treatment-related, noncancer cause of death in childhood cancer survivors. Increasingly, molecularly targeted agents, including small molecule inhibitors, are being incorporated into pediatric oncology. The acute and chronic risks associated with these newer therapeutic options in children are not yet well-described, which poses challenges for clinicians caring for these patients. In the present review, the unique risks factors, prevention strategies, and treatment of cardiovascular toxicities of the child with cancer and the childhood cancer survivor are examined, with an emphasis on the perioperative period. [ABSTRACT FROM AUTHOR]

Background: Patients receiving anthracycline-based chemotherapy (AbC) for newly diagnosed diffuse large B-cell lymphoma (DLBCL) may develop cardiac electrophysiological abnormalities. In this study, their electrocardiography (ECG) features were analyzed.Methods: Electronic health records of patients with a diagnosis of DLBCL and treated with AbC were reviewed retrospectively. Variables from ECGs obtained around anthracycline treatment were manually measured.Results: A total of 76 patients (57% males). The incidence of abnormal ECG increased from 36.8% at baseline to 48.7%, of which only the prevalence of fragmented QRS (fQRS) significantly increased after AbC (15.8% to 28.9%, P = 0.041). In comparison with baseline ECG parameters, corrected QT interval (QTc) statistically prolonged (399.95 ± 27.11 ms to 415.07 ± 31.03 ms, P < 0.001), whilst QT dispersion (QTd) significantly (41.25 ± 16.15 ms to 36.70 ± 11.84 ms, P = 0.032) decreased.Conclusion: In DLBCL patients receiving anthracycline-based therapies, the main ECG abnormalities detected were fQRS and QTc prolongation. Regular ECG monitoring should be carefully performed on follow-up to detect cardiotoxicity during follow-up after treatment. [ABSTRACT FROM AUTHOR]

More than half of patients with soft tissue sarcoma (STS) are aged ≥65 years (older), however contemporary data on the efficacy/safety of anthracycline chemotherapy in older patients with STS are lacking. SARC021 randomized patients to receive first-line doxorubicin or doxorubicin plus evofosfamide. The main aim of this study was to compare the outcome and safety of first-line anthracycline-based therapy in older patients compared with those <65 years. IRB approval was obtained at all participating sites and this research meets requirements for protection of human subjects. Of 640 patients, 209 (33%) were older, with a median age 70 (range 65–89) years. The median overall survival (OS) was 16.7 months (95%CI: 13.2–20.0) in older patients compared to 20.1 months (95%CI: 16.9–23.2) in those aged <65 years (n = 431), HR 1.21 (95%CI: 0.99–1.48), p =.057. The median progression-free survival (PFS) in older patients was 6.3 months (95%CI: 5.8–7.2) compared to 6.0 (95%CI: 5.1–6.4) in those <65 years, HR 0.86 (95%CI: 0.70–1.05), p =.14. Older patients had significantly more hematological (141 [67%] versus 208 [48%], p <.0001), non-hematological (131 [63%] versus 215 [50%], p =.0097) and ≥ Grade 3 adverse events (178 [85%] versus 299 [69%], p =.0002), compared to younger patients. More older patients (30, 14%) stopped treatment due to adverse events compared to younger patients (22, 5%), p =.0001. The efficacy of first-line anthracycline-based chemotherapy did not differ significantly between older and younger advanced sarcoma patients. Significantly more older patients stopped chemotherapy due to adverse events. These results provide a benchmark for daily clinical practice and future trials in older patients. [ABSTRACT FROM AUTHOR]

Valvular heart diseases (VHD) may be observed in patients with cancer for several reasons, including preexisting valve lesions, radiotherapy, infective endocarditis, and secondary to the left ventricle dysfunction. The incidence of VHD is especially in younger survivors treated with thoracic radiation therapy for certain malignancies, such as Hodgkin's lymphoma and breast cancer. The mechanism of radiation-induced damage to heart valves is not clear and includes diffuse fibrocalcific thickening of the valve. VHD is commonly diagnosed after a long latent period, in the context of clinical symptoms, or suspected on the basis of a new murmur. The evaluation includes identification of anatomical valve abnormalities, valve dysfunction, and assessing the functional consequences of valve dysfunction on the ventricles. Echocardiography is the optimal imaging technique for diagnostic and therapeutic management. Cardiovascular magnetic resonance and computed tomography (CT) may be used to assess the severity of VHD, but cardiac CT is mainly useful for detecting extensive calcifications of the ascending aorta. Patients exposed to mediastinal radiotherapy and minimal valve dysfunction require follow-up of 2–3 years, with moderate valve disease yearly, with severe, should be assessed for valve surgery. [ABSTRACT FROM AUTHOR]

It is important to determine whether anthracycline-containing regimens or taxane-containing regimens are more effective in individual patients. The present study compared the efficacy of six cycles of docetaxel and cyclophosphamide (TC6) with that of three cycles of 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel (FEC-D) in Japanese patients with hormone receptor (HR)-negative breast cancer (BC) to identify subtypes requiring anthracycline treatment. The study included 103 patients with operable HR-negative BC. Of these patients 53 received FEC-D and 50 received TC6. The primary endpoint was pathological complete response (pCR). The secondary endpoints were safety, breast-conserving surgery, disease-free survival (DFS) and overall survival (OS). The predictive factors for each regimen were evaluated. Of the 103 patients, 97 completed the study (FEC-D, 50 patients; TC6, 47 patients). The pCR rate was higher with FEC-D (36%) than with TC6 (25.5%); however, the difference was not significant (P = 0.265). TC6 was safer than FEC-D, as the adverse events with docetaxel in the FEC-D regimen were similar to those with the TC6 regimen. Among patients with basal BC, the pCR rate was significantly higher with FEC-D (42.9%) than with TC6 (13.6%; P = 0.033). Among patients with triple-negative breast cancer (TNBC), the DFS and OS were significantly better with FEC-D than with TC6 (P = 0.016 and P = 0.034, respectively). TC6 was not as effective as FEC-D for treating HR-negative BC, as TC6 was not sufficient to treat TNBC, particularly the basal subtype. Our findings suggest that anthracyclines are better treatment options than taxanes for basal BC. • The pCR rate was higher with FEC-D than with TC6 (P = 0.265). • For basal BC, the pCR rate was higher with FEC-D than with TC6 (P = 0.033). • For TNBC, DFS and OS were better with FEC-D than with TC6 (P = 0.016 and P = 0.034). [ABSTRACT FROM AUTHOR]

• Radiation therapy (RT) and anthracycline increase cardiovascular (CV) risk in breast cancer patients. • Concomitant use of Left-side RT and doxorubicin ≥250 mg/m2 increased CV risk. • CV disease screening is important in those breast cancer patients. Cancer treatment increases the risk of cardiovascular (CV) events. However, the long-term CV outcome of breast cancer patients who undergo radiotherapy and chemotherapy concomitantly is unknown. This study aimed to determine the incidence and risk factors of CV events among these patients. Six hundred sixty consecutive breast cancer patients older than 50 years from November 2005 to September 2015, were enrolled in four university hospitals. The primary endpoint was CV events including CV mortality, myocardial infarction, heart failure, and stroke. CV events occurred in 14 (2.1%) patients during the follow-up period (median, 47.1 months). Left-side irradiation was associated with increased risk of CV events in patients with doxorubicin dose ≥250 mg/m2 but not in patients with doxorubicin dose <250 mg/m2. On multivariable analysis, concomitant left-side irradiation with doxorubicin dose ≥250 mg/m2 and hypertension were independent risk factors for CV events. The risk of CV events was further increased with concomitant left-side irradiation and doxorubicin ≥250 mg/m2 in breast cancer patients. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. Background Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. Methods A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m 2 ), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τ ic ; a marker of cardiomyocyte size), and late gadolinium enhancement. Results At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m 2 ), a mean ECV of 0.32 ± 0.038, mean τ ic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m 2 ), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m 2 to 36 ± 6 g/m 2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τ ic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τ ic (β = 4.1 ± 1.5 g/m 2 per 100-ms increase in τ ic , p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 − ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. Conclusions A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036 ) [ABSTRACT FROM AUTHOR]

Anthracycline is a standard drug for the treatment of breast cancer. However, anthracycline has great cardiotoxicity. Some patients stop chemotherapy during severe chemotherapy and even undergo serious heart failure. At the same time, there is lack of clinical study on whether aerobic exercise can reduce the cardiotoxicity of chemotherapy drugs. The purpose of this study is to investigate the effects of aerobic exercise on the cardiac function of patients with breast cancer after anthracycline therapy. The results showed that the control group LVEF decreased significantly. In addition, the E/A value decreased and the DT interval prolonged in the control group, show that anthracycline on myocardial damage, and the observation group LVEF increased significantly (P<0.05), the results show that aerobic exercise can improve heart function, and to a certain extent, it could reverse the damage of chemotherapy drugs on the heart. [ABSTRACT FROM AUTHOR]

Objectives To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA). Materials and Methods Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as biomarkers were analyzed for association with clinical outcome within the randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN) trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine. Results Of 210 patients, 38% were > 65 years old. GA (n = 152) classified 74% as fit, 10% as compromised, and 16% as frail. Biomarkers showed no age dependency. In multivariate analysis (n = 70) KPS, GA, cumulative illness rating scale-geriatrics (CIRS-G), and GPS were significantly associated with time to progression, and KPS, CIRS-G, and instrumental activities of daily living (IADL) from GA, and PINI showed a significant correlation with overall survival. Conclusion GA evaluation was feasible. KPS significantly correlated with efficacy outcomes. Items of a GA and biomarkers of inflammation and nutrition may have prognostic significance in patients with MBC. [ABSTRACT FROM AUTHOR]

Nanocarriers bearing anticancer drugs are promising candidates to improve the efficacy of cancer therapy and minimize side effects. The most potent cytostatics used in the treatment of various cancers are anthracyclines, e.g. doxorubicin or pirarubicin. Recently, polymer therapeutics carrying anthracyclines have been intensively studied. The precise characterization of in vitro nanocarrier biological behavior brings a better understanding of the nanocarrier characteristics and enables prediction of the behavior of the nanocarrier during in vivo application. Advanced fluorescence detection methods, e.g. fluorescence lifetime imaging microscopy (FLIM), were successfully exploited to describe the properties of various polymeric nano-systems and contributed to a complex view of anthracyclines' intracellular transport and DNA intercalation. Here, we report the application of a specific technique for processing FLIM images, called fluorescence pattern decomposition, to evaluate early events after doxorubicin or pirarubicin treatment of cells. Moreover, we characterized changes in the intracellular localization and release of the anthracyclines during the incubation of cells with polymer nanotherapeutics based on poly[N-(2-hydroxypropyl)- methacrylamide] (pHPMA). [ABSTRACT FROM AUTHOR]

With ongoing advancements in cancer-related treatments, the number of cancer survivors continues to grow globally, with numbers in the United States predicted to reach 18 million by 2020. As a result, it is expected that a greater number of patients will present with chemotherapy-related side effects. One entity in particular, chemotherapy-related cardiomyopathy (CCMP), is a known cardiotoxic manifestation associated with agents such as anthracyclines, trastuzumab, and tyrosine kinase inhibitors. Although such effects have been described in the medical literature for decades, concrete strategies for screening, prevention, and management of CCMP continue to be elusive owing to limited studies. Late recognition of CCMP is associated with a poorer prognosis, including a lack of clinical response to pharmacologic therapy, and end-stage heart failure. A number of advanced cardiac therapies, including cardiac resynchronization therapy, ventricular assist devices, and orthotopic cardiac transplantation, are available to for end-stage heart failure; however, the role of these therapies in CCMP is unclear. In this review, management of end-stage CCMP with the use of advanced therapies and their respective effectiveness are discussed, as well as clinical characteristics of patients undergoing these treatments. The relative paucity of data in this field highlights the importance and need for larger-scale longitudinal studies and long-term registries tracking the outcomes of cancer survivors who have received cardiotoxic cancer therapy to determine the overall incidence of end-stage CCMP, as well as prognostic factors that will ultimately guide such patients toward receiving appropriate end-stage care. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APML) is considered to be sensitive to all-trans-retinoic acid (ATRA) which acts as a differentiating agent. ATRA is considered to be a well-tolerated agent and is known to achieve complete remission in acute promyelocytic leukemia. However, a few cases on long term all-trans-retinoic acid (ATRA) use can develop pseudotumor cerebri. Out of 32 patients with APML who were treated in our Centre over a 4-year-period, we encountered 6 patients who developed ATRA-related pseudotumor cerebri while on maintenance treatment. The patients ranged from 12 to 40 years of age. 3 patients complained of unbearable headache, 2 of diplopia and 1 of gross reduction in visual acuity. CT scans and MRI did not reveal any intracranial lesions. Cerebrospinal fluid (CSF) examination was normal with CSF manometry revealing a high CSF pressure (average of 345mmH2O). Fundoscopy revealed papilledema in 5 patients and optic atrophy in 1 patient. The patients were successfully managed with decrease dose/discontinuation of ATRA, use of acetazolamide, corticosteroids and therapeutic CSF drainage. [ABSTRACT FROM AUTHOR]

Anthracyclines, e.g. doxorubicin, pirarubicin, are widely used as cytostatic agents in the polymer nanotherapeutics designed for the highly effective antitumor therapy with reduced side effects. However, their precise dosage scheme needs to be optimized, which requires an accurate method for their quantification on the cellular level in vitro during nanocarrier development and in body fluids and tissues during testing in vivo. Various methods detecting the anthracycline content in biological samples have already been designed. Most of them are highly demanding and they differ in exactness and reproducibility. The cellular uptake and localization is predominantly observed and determined by microscopy techniques, the anthracycline content is usually quantified by chromatographic analysis using fluorescence detection. We reviewed and compared published methods concerning the detection of anthracycline nanocarriers. [ABSTRACT FROM AUTHOR]

Since the introduction of all-trans-retinoic acid, the use of this molecularly targeted treatment in combination with anthracycline-based chemotherapy has completely changed the prognosis of acute promyelocytic leukemia (APL) turning it into the most curable acute myeloid leukemia. Also, the use of risk-adapted protocols has optimized the drug combination and the most appropriate dose intensity for each subset of patients classified according to both risk of relapse and vulnerability to drug toxicity. Recent developments have included the investigation of the role of arsenic trioxide (ATO) as front-line treatment after its success in relapsed APL, both to minimize or even omit the use of cytotoxic agents and to reinforce the conventional chemotherapy-based approach. In the present chapter we will address the achievements of conventional treatment with ATRA and chemotherapy, as well as the opportunity to cure more patients with modifications of this therapeutic backbone with the addition of ATO in any phase of treatment. [Copyright &y& Elsevier]

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Abstract: Objective: To investigate the predictive and prognostic value of topoisomerase IIα (Topo IIα, Topo II) expression in the primary tumors and residual tumors of local advanced breast cancer (LABC) patients being treated with anthracycline-based neoadjuvant chemotherapy (NCT). Methods: The data from 283 LABC patients who had been treated with anthracycline-based neoadjuvant chemotherapy were collected. The expression of Topo IIα, HER-2 and other biomarkers was determined via immunohistochemical analysis in pre- and post-chemotherapy specimens. The status of pre-treatment biomarkers was correlated with the clinical response determined by the RECIST 1.1 criteria, whereas the post-treatment biomarkers were studied for prognostic value using the Cox model. Results: By analyzing the complete data from 99 patients, the co-expression of HER-2/Topo IIα was found to be significantly correlated with the clinical response to chemotherapy (Logistic regression P = 0.042). Notably, a 20% alteration in the Topo IIα status during neoadjuvant chemotherapy was found, which could also influence the sensitivity to treatment. With a survival analysis performed in 245 patients with residual tumors after NCT, node metastasis, HER-2 and Ki-67 were independent predictors of patient outcome. However, post-treatment Topo IIα expression demonstrated significant prognostic value in HER-2+ patients (P = 0.002). A relatively lower disease-free survival and overall survival was observed in HER-2+/Topo- patients (log rank P = 0.010 for DFS and P < 0.001 for OS). Conclusion: Topo IIα, together with HER-2, might help to select for patients who could benefit from anthracycline-based neoadjuvant chemotherapy and identify non-complete responders at a higher risk of disease recurrence or death. [Copyright &y& Elsevier]

Abstract: Setting up the correct functionality with the correct stereochemistry in the ring-A of anthracycline precursors represents a synthetic challenge. The use of d-glucose as a chiral auxiliary either on the silyloxy diene or naphthoquinone-based dienophile to form the ring-A using asymmetric Diels–Alder reactions as developed by the Stoodley group and is the focus of this review. The endo-transition state is described based on a frontier orbital approach and the HOMO–LUMO energy gaps were estimated using semi-empirical (MNDO) calculations with SPARTAN’08. As anthracyclines are used in chemotherapy, some of their associated biochemistry and clinical effectiveness are also briefly introduced. [Copyright &y& Elsevier]

Abstract: Background: Recent studies suggest that older women derive similar benefits from adjuvant systemic chemotherapy (AST) as younger women. In older women, the ability to successfully complete chemotherapy may be complicated by other health conditions and performance status. We examined factors affecting the delivery of chemotherapy to older patients with breast cancer. Methods: Women age ≥65 treated with adjuvant/neoadjuvant chemotherapy at Roswell Park Cancer Institute were identified from the RPCI database from 7/1997 to 4/2010. Endpoints were delay, hospitalization, dose reduction, relative dose intensity (RDI) <85%, and incomplete administration of chemotherapy. Data recorded included medical comorbidities and the use of anthracycline-based chemotherapy. The Pearson chi-squared, Wilcoxon rank sum, logistic regression, Kaplan–Meier, and log-rank tests were used to analyze outcomes. A 0.05 nominal significance level was used in all testing. Results: 204 older women received AST. Median follow-up was 50.2months. Seventy percent received anthracycline-based AST. In multivariate analysis, older age was a predictor for early termination of chemotherapy and RDI <85%. Hypertension was correlated with delay and hospitalization. A Charlson comorbidity index ≥1 and anthracycline-based chemotherapy regimens were associated with chemotherapy delays. The successful completion of chemotherapy and the delivery of a RDI ≥85% of planned chemotherapy were associated with improved survival (p=0.01, and p<0.01 respectively). Significant toxicity resulting in a change in therapy or schedule occurred in 45% of cases. Conclusion: Successful administration of planned chemotherapy to older women with breast cancer was associated with improved OS. However, delivery of chemotherapy was associated with increased toxicity and reduced tolerance. Models allowing physicians to better risk-stratify older patients with breast cancer are needed and under development. [Copyright &y& Elsevier]

Summary: Tumor biomarkers increasingly provide information for predicting outcomes with chemotherapeutic regimens (personalized medicine). Topo2A is a DNA helicase targeted by anthracyclines, cytotoxic therapeutics used in both adjuvant and palliative treatments of breast cancer. TOP2A gene amplification/deletion is implicated in response to anthracycline-based chemotherapy. We describe an approach for analyzing formalin-fixed, paraffin-embedded breast tumors on tissue microarrays with TOP2A fluorescence in situ hybridization coupled with cytokeratin immunofluorescence to target tumor cells. Stained tissue from patient specimens was imaged and analyzed using Metafer/Metacyte (Metasystems, Waltham, MA, USA), including customized image classifiers. TOP2A/CEN17 ratios of 2.0 or greater (amplified) and 0.8 or less (deleted) were observed for 10.0% and 6.1% of the patients, respectively. Patient outcomes for adjuvant chemotherapy (cyclophosphamide-epirubicin-fluorouracil, cyclophosphamide-methotrexate-fluorouracil, no chemotherapy) were evaluated. No statistical significance was achieved for clinical end points regarding TOP2A status in anthracycline-treated patients. However, patients with TOP2A aberrations receiving methotrexate-based therapy exhibited a significant decrease in 5-year distant disease-free survival and breast cancer–specific overall survival, especially for patients with TOP2A deletions (disease-free survival: hazard ratio, 5.31 [P = .001], and breast cancer–specific overall survival: hazard ratio, 6.45 [P ≤ .001]). No significant differences were seen in patients included in the no-chemotherapy group. Topo2A protein levels were assessed by immunohistochemistry with no correlative statistical relevance to immunofluorescence/fluorescence in situ hybridization–based prognosis for cyclophosphamide-epirubicin-fluorouracil or cyclophosphamide-methotrexate-fluorouracil groups. Interestingly, aberrant (under)expressing patients in the no-chemotherapy group exhibited better 5-year distant disease-free survival (hazard ratio, 0.39; P = .004), trending toward more favorable breast cancer–specific overall survival (hazard ratio, 0.61; P = .11). Our results indicate a strategy by which fluorescence in situ hybridization scoring targeted to cytokeratin-positive tumor cells may provide a tool for added precision and efficiency in TOP2A evaluation from tumor tissue. [Copyright &y& Elsevier]

Copyright of Journal of Cardiovascular Echography is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background: Topoisomerase II-α is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-α expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-α overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients. Material and methods: Topoisomerase II-α, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-α status and dose intensity. Results: Tumors from 40 patients (36%) showed topoisomerase II-α overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-α expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-α (P =0.010 and 0.027, respectively). Negative PR (P =0.041), positive HER2 (P =0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-α negative shown no significance (HR=0.92, IC 95% 0.39–2.15, P =0.839) while the multivariate analysis in topoisomerase II-α positive, dose intensity shown to be statistically significant (HR=2.725, IC 95% 1.07–6.95, P =0.036). Conclusions: Our data do not support a correlation between topoisomerase II-α expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-α may experience better clinical benefit with higher anthracycline dose intensity. [Copyright &y& Elsevier]

Abstract: Background: One can consider as a standard neoadjuvant treatment for breast cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel. Based on the belief that the sequence order between anthracycline and taxane might be of interest, this study assessed the impact of the sequence order. Methods: One hundred and twenty three patients with breast cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between 2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus another cohort of 58 patients treated with 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (cohort A). Results: The overall dose intensity of docetaxel and clinical complete responses were significantly higher in cohort T. No statistically significant differences were observed in terms of conservative surgeries or histological responses. The sequence of chemotherapy did not significantly influence other treatment-related toxicities. Mild neurotoxicity was higher in patients treated in cohort T. Anemias (≥Grade 1) were higher in cohort A (52% versus 81%; p = 0.0008). Conclusion: The present study failed to identify an impact of the sequence of taxane administration on the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces the occurrence of anemia. These findings might allow a selection of the sequence order based on the toxicity profile. [Copyright &y& Elsevier]

Summary: Human epidermal growth factor receptor-2 (HER-2) and topoisomerase IIα (topo IIα) co-inhabit chromosome 17. In the search for predictive biomarkers to refine clinical prescription of cytotoxic agents, both HER-2 and topo IIα are under exploration for their potential role in identifying individuals with early breast cancer who may benefit from anthracycline therapy. Whilst recent meta-analyses support a predictive role for HER-2 amplification, it remains unclear whether HER-2 is the critical biomarker or whether it is a surrogate marker for topo IIα alteration, a known drug target of anthracyclines. The major limitation in considering HER-2 as a single marker is heterogeneity within the subgroups of HER-2 positive and HER-2 negative disease. For topo IIα, current data is inconclusive. Issues plaguing this field are technical variability in marker definition, complex regulation pathway of topo IIα and lack of prospective, adequately powered studies. With current evidence, neither HER-2 nor topo IIα gene status can be considered clinically valuable markers for anthracycline benefit. This paper will focus on issues relating to reliable detection and predictive analyses of HER-2 and topo IIα, and highlight potential developments in improving individualized approach to anthracycline use in early breast cancer patients. [Copyright &y& Elsevier]

Abstract: Anthracyclines are valuable cytotoxic agents in cancer treatment. However, their usefulness is limited by cumulative dose-dependent cardiotoxicity that may manifest as life-threatening congestive heart failure. To avoid cardiotoxicity, the use of doxorubicin is typically capped at a safe cumulative dose. Liposomal formulations may reduce cardiac risks whilst maintaining anti-cancer efficacy. Efficacy and safety studies of non-pegylated liposomal doxorubicin (NPLD) in metastatic breast cancer (MBC) are reviewed, along with studies that examine efficacy and cardiac tolerability in combination with newer agents such as paclitaxel and trastuzumab. These show that cardiac safety of liposomal doxorubicin is similar to that of epirubicin in cumulative dose, but that the formulation, unlike epirubicin, has similar anti-cancer efficacy to doxorubicin at equimolar doses. Liposomal doxorubicin may have a better therapeutic index than non-liposomal anthracyclines. This justifies further studies in patients where cumulative cardiotoxicity is a concern, as does study of its use with other potentially cardiotoxic agents. [Copyright &y& Elsevier]

Ovarian carcinosarcoma (OCS) is a rare malignancy associated with a poor prognosis. Platinum, anthracyclines, and alkylating agents are the most effective antiblastic drugs for treatment of gynecologic epithelial and stromal tumors. The aim of this study was to determine response rate and overall survival (OS) of patients with OCS who were treated with a combination of these 3 drugs.Forty-one women with OCS who were referred to the Department of Gynecologic Oncology of San Gerardo Hospital in Monza and European Institute of Oncology in Milan, between January 1995, and December 2006, and treated with a combination regimen of cisplatin, adriamycin, and cyclophosphamide or a combination regimen containing of cisplatin, epirubicin, and ifosfamide plus granulocyte colony-stimulating factor were considered for this study.Four women had OCS stage I; 7, stage II; 23, stage III; and 7, stage IV. Heterologous, homologous, and mixed stromal components were described in 17, 14, and 10 patients, respectively. Thirteen women were treated with a combination of cisplatin, adriamycin, and cyclophosphamide and 28 with a combination of cisplatin, epirubicin, and ifosfamide plus granulocyte colony-stimulating factor. Two women did not complete their treatment because of the rapid progression of their disease and severe toxicity. Among 22 women considered evaluable for response, 10 (46%) achieved a complete response and 3 (13%) achieved a partial response (global response rate, 59%). Overall progression-free survival was 11.8 months (range, 0.9-96 months) and 13.8 and 10.1 months in stage I-II and III-IV, respectively (P = 0.13). Median OS was 20 months (range, 1-123 months), not reached in stage I-II, and 19.7 months in stage III-IV (P = 0.07). No significant difference between homologous and heterologous sarcomatous components was observed (P = 0.95), whereas no significant trend of improved OS was noticed for stage IIIC-IV with optimal debulking surgery (n = 9), compared with suboptimal cytoreduction (n = 19; 32.6 vs 14.5 months, P = 0.14).The combination of anthracycline, alkylating agent, and cisplatin showed a good response rate but also a high toxicity. The prognosis of OCS remains poor. Optimal cytoreduction may improve survival, but new anticancer drugs or more effective regimens are awaited. [ABSTRACT FROM AUTHOR]

The article focuses on the efficacy of trastuzumab, its potential for cardiac compromise, and its interaction with anthracyclines. The biological mechanisms that might be responsible for cardiotoxicity are highlighted. It discusses the optimal usage of the drugs to minimize the risk of cardiotoxicity, and its treatment. Also noted are alternatives to anthracycline-trastuzumab regimens.

Purpose: The purpose of this retrospective analysis was to describe the clinical course of patients with breast cancer with liver metastases alone who were treated on doxorubicin/cyclophosphamide or taxane-containing chemotherapy protocols at the M. D. Anderson Cancer Center. Patients and Methods: A total of 2,193 patients with metastatic breast cancer were treated on prospective clinical protocols at the University of Texas M. D. Anderson Cancer between 1973 and 2003. Among those, 132 were identified as having the liver as the first site of metastatic disease. The following information was obtained from the medical records: gender, age, race, performance status, menopausal status, hormonal receptor status, laboratory data, primary treatment, prior systemic treatment, disease-free interval, extent of metastatic disease, response to chemotherapy, site of progression, time to tumor progression, overall survival, and cause of death. Results: Of the patients 62% received anthracycline-based regimens and 38% received anthracycline- and taxane-based regimens on various clinical protocols as the initial therapy for metastatic disease. The median follow-up of the patients was 52 months. The overall objective response rate was 66.4%; 16.4% of the patients achieved complete responses. The median time to progression was 14 months. Progression-free survival rates were 56% and 30% at 12 and 24 months, respectively. The median overall survival was 25 months. Sixteen patients (12.1%) survived longer than 60 months. There was a statistically inverse relation between a high lactate dehydrogenase level and achieving a complete response (P < 0.05). Age ->50 years, extent of liver metastases, performance status, and lactate dehydrogenase and albumin levels are significantly related to progressionfree survival (P < 0.05). Year of liver metastases diagnosis, extent of liver metastases, performance status, and albumin level are significantly related to overall survival (P < 0.05). Conclusions: This retrospective analysis demonstrated that patients with liver metastases only had high objective response rates and encouraging results for median survival obtained with currently available cytotoxic agents. [ABSTRACT FROM AUTHOR]

ABSTRACT: Metastatic breast cancer (MBC) remains an incurable disease. The aims of treatment include tumour shrinkage, symptom control, delay of disease progression and prolongation of survival while maintaining an acceptable quality of life. In the last decade, a decline in mortality has been observed. Combination chemotherapy generally provides some survival advantage over single-agent chemotherapy. Taxanes and antimetabolites are among the most effective agents, providing a balance between efficacy and tolerability. Increasing numbers of patients are receiving adjuvant anthracycline and taxane therapy. In these patients, treatment options include cytotoxic agents not used in adjuvant treatment, re-challenge with anthracycline and taxanes, or new targeted agents such as pertuzumab, lapatinib or bevacizumab. Biology of the disease at cell level plays a major role in treatment choice. Key points in the intracellular signal transduction pathways relevant for cell proliferation, apoptosis and the angiogenesis/metastasis process, represent possible targets for new target-specific agents. Tailored therapies are a step forward in improving patients'' prognosis. [Copyright &y& Elsevier]

Summary: We evaluated the efficacy and safety of the combination of docetaxel and cisplatin in metastatic breast cancer (MBC) patients previously treated with anthracycline-containing regimens. Between June 1999 and December 2002, 50 female MBC patients (median age 43 years; range 29–64) received docetaxel 75mg/m2 and cisplatin 75mg/m2 on day 1 of each 4-week cycle. A total of 226 cycles (median four cycles per patient) were administered as first-line (23 patients) or second-line (27 patients) treatment. Five patients (10%) achieved a complete response (CR) and 15 (30%) had partial responses (PR), giving an overall response rate of 40% (95% CI, 26.4∼53.6%). The median duration of response was 6.1 months (range, 2.3∼29.2+ months). With a median follow-up of 15.9 months, median time to progression was 6.2 months (range 1∼22.5+ months). Toxicities included grades III and IV neutropenia in nine (18%) and ten (20%) patients, respectively, and febrile neutropenia in seven patients (14%). In conclusion, our data show that docetaxel plus cisplatin is effective with the manageable toxicity profile in MBC patients previously treated with anthracyclines. [Copyright &y& Elsevier]

Summary: Follicular lymphoma (FL) is a malignancy of follicle centre B cells that have at least a partially follicular pattern, and is the commonest type of indolent Non-Hodgkin’s lymphoma. Except in the subset of patients with localized disease, FL should still be regarded as an incurable malignancy with a relentless relapsing/remitting course. However, the provocative new data covered by this review (including anti-CD20 antibody therapy, BCL-2, radioimmunotherapy, new chemotherapeutic agents and anti-idiotype vaccination), provides much cause for excitement and guarded optimism. Rituximab represents a novel treatment approach for a variety of disease settings, with a proven excellent efficacy and toxicity profile. Long-term data is required to establish whether its use translates into survival benefit. As the clinical activity of rituximab and other new therapeutic approaches becomes established, it will be important to determine how best to integrate these results into the standard care of patients with follicular lymphoma. [Copyright &y& Elsevier]

Copyright of West Indian Medical Journal is the property of West Indian Medical Journal (WIMJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Doxorubicin (DOX) is a highly potent anti-neoplastic agent, which is widely used in clinical practice; however, its dosage and duration of administration are strictly limited due to dose-related cardiac damage. The present study investigated whether theanine, an amino acid found in green tea leaves, can reduce DOX-induced acute cardiotoxicity by examining changes in serum enzyme activities. The activities of creatine kinase (CK) and lactate dehydrogenase (LDH), biochemical markers of cardiac impairment, in serum were elevated by the administration of 20mg/kg DOX to mice. Elevations in serum enzyme activities were attenuated by concurrent treatment with theanine, and significant suppression was observed at a dose of 10mg/kg, which is comparable to daily intake in the form of supplement. Especially, CK activity was recovered by theanine almost to control levels. Body weight loss caused by DOX was significantly suppressed by theanine treatment. These results suggest that theanine can protect against DOX-induced acute cardiac injury. [Copyright &y& Elsevier]

To assess the safety and efficacy of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline chemotherapy-induced nausea and vomiting. One hundred patients with breast cancer from department of Medical Oncology of Ordos Central Hospital from June 2015 to February 2018 were selected and randomize subdivided into 2 groups. All cases received anthracycline (30 mg/m2/d for pirarubicin or 45 mg/m2/d for epirubicin) and cyclophosphamide adjuvant chemotherapy, along with either the standard therapy (dexamethasone and tropisetron) or the combined aprepitant therapy (aprepitant plus dexamethasone and tropisetron). The results of the observation between groups were presented by complete response in the overall phase (OP, 0-120 hours), acute phase (AP, 0-24 hours) and delay phase (DP, 25-120 hours). The Kaplan-Meier curves were plotted to exhibit the first time of vomiting, Functional Living Index-Emesis of patients' quality of life, and therapy-related adverse effects (AEs). The complete response of OP, AP, and DP were statistically different between aprepitant group and standard group (80.0% vs 48%, P = 0.001; 92.0% vs 74%, P = 0.017; 80.0% vs 48%, P = 0.001). The aprepitant group held a longer time reaching the first emesis after the relevant treatment than the standard group. The Functional Living Index-Emesis increased significantly in the aprepitant group compared with the standard group (24% vs 8.3%, P = 0.029). Fatigue and constipation were the only AEs of aprepitant, since no significant differences were observed in fatigue between the 2 groups (72% vs 70%, P = 0.826), while the incidence of constipation of aprepitant group was higher than the standard group (48% vs 28%, P = 0.039). Combined aprepitant therapy is efficient and safe in the multiple-day anthracycline chemotherapy-induced nausea and vomiting control and is recommended for the clinical use. [ABSTRACT FROM AUTHOR]

Administering trastuzumab after a course of anthracycline therapy for breast cancer can result in cardiac toxicity. Serial echocardiograms in this study showed that a lower initial left ventricular ejection fraction before anthracycline therapy and the amount of decrease in ejection fraction after the anthracycline course are predictive of subsequent trastuzumab cardiac toxicity. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear. Methods and Results: Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1–25 mg/kg), revealing a dose-dependent decrease in cardiac mass (R 2=0.64; P <0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336±29 versus 188±14 µm2; P <0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R2=0.91; P =0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg/kg to mice lacking MuRF1 (MuRF1−/−) and wild-type littermates. MuRF1−/− mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation. Conclusions: Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines. [ABSTRACT FROM AUTHOR]