ABSTRACT

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

PMID:37889193 | DOI:10.1161/JAHA.123.029574

00:04

PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Front Pharmacol. 2023 Oct 4;14:1263975. doi: 10.3389/fphar.2023.1263975. eCollection 2023.

ABSTRACT

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

PMID:37860116 | PMC:PMC10582335 | DOI:10.3389/fphar.2023.1263975

00:04

PubMed articles on: Cardio-Oncology

Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy

Curr Oncol. 2023 Oct 6;30(10):9049-9062. doi: 10.3390/curroncol30100654.