ABSTRACT

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

PMID:37746544 | PMC:PMC10516830 | DOI:10.1007/s12291-022-01075-3

06:07

PubMed articles on: Cardio-Oncology

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial

Circulation. 2023 Sep 25. doi: 10.1161/CIRCULATIONAHA.123.064274. Online ahead of print.

ABSTRACT

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.

METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%.

RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent).

CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline.

REGISTRATION: URL: https://doi.org/10.1186/ISRCTN24439460; Unique identifier, ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-000896-99; Unique identifier: EudraCT 2017-000896-99.

PMID:37746692 | DOI:10.1161/CIRCULATIONAHA.123.064274

06:07

PubMed articles on: Cardio-Oncology

The Effects of Drug Exposure and SNPs on Aaptinib-induced Severe Toxicities in Solid Tumors

Drug Metab Dispos. 2023 Sep 29:DMD-AR-2023-001428. doi: 10.1124/dmd.123.001428. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities.

METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed.

RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P＜0.01; M1-1: P＜0.01) and high-grade anti-angiogenetic toxicities (APA: P = 0.034; P＜0.05), including hypertension, proteinuria and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P＜0.001) and M1-1 (P＜0.01) while CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P＜0.01).

CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need considering in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. Significance Statement Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

PMID:37775332 | DOI:10.1124/dmd.123.001428

06:07

PubMed articles on: Cardio-Oncology

Altered Peripheral Blood Gene Expression in Childhood Cancer Survivors With Anthracycline-Induced Cardiomyopathy - A COG-ALTE03N1 Report

J Am Heart Assoc. 2023 Oct 3;12(19):e029954. doi: 10.1161/JAHA.123.029954. Epub 2023 Sep 26.