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2/19/26

ABSTRACT

BACKGROUND: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug-drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy.

METHODS: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated.

RESULTS: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient's home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068).

CONCLUSIONS: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors.

PMID:37760556 | DOI:10.3390/cancers15184587

20:29

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

20:29

PubMed articles on: Cancer & VTE/PE

Early identification of lung cancer patients with venous thromboembolism: development and validation of a risk prediction model

Thromb J. 2023 Sep 14;21(1):95. doi: 10.1186/s12959-023-00544-w.

ABSTRACT

INTRODUCTION: Venous thromboembolism(VTE) is a leading cause of death in patients with lung cancer. Furthermore, hospitalization of patients with advanced lung cancer for VTE treatment represents a major economic burden on the national public health resources. Therefore, we performed this prospective study to identify clinical biomarkers for the early identification of VTE in lung cancer patients.

METHODS: This prospective study enrolled 158 patients with confirmed lung cancer, including 27 who were diagnosed with VTE within six months of the follow-up after lung cancer diagnosis. Multivariate logistic regression analysis was used to evaluate the diagnostic performancese of all the relevant clinical features and laboratory indicators in identifying lung cancer patients with a higher risk of VTE. A novel risk prediction model was constructed consisting of five clinical variables with the best diagnostic performances and was validated using the receiver operation characteristic(ROC) curves. The diagnostic performances of the new risk prediction model was also compared with the Khorana risk score (KRS) and the Padua risk score (PRS).

RESULTS: The VTE group of lung cancer patients (n = 27) showed significantly higher serum levels of fibrin degradation products (FDP), D-dimer, thrombomodulin (TM), thrombin-antithrombin-complex (TAT), α2-plasmin inhibitor-plasmin Complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) compared to those in the non-VTE group (n = 131). ROC curve analyses showed that the diagnostic efficacy of the new VTE risk prediction model with TM ≥ 9.75 TU/ml, TAT ≥ 2.25ng/ml, t-PAIC ≥ 7.35ng/ml, history of VTE, and ECOG PS score ≥ 2 was superior than the KRS and the PRS in the early identification of lung cancer patients with a higher risk of VTE.

CONCLUSIONS: The new risk prediction model showed significantly high diagnostic efficacy in the early identification of lung cancer patients with a high risk of VTE. The diagnostic efficacy of the new risk prediction model was higher than the KRS and the PRS in this cohort of lung cancer patients.

PMID:37710256 | PMC:PMC10500728 | DOI:10.1186/s12959-023-00544-w

20:29

PubMed articles on: Cardio-Oncology

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity

Indian J Clin Biochem. 2023 Oct;38(4):536-540. doi: 10.1007/s12291-022-01075-3. Epub 2022 Sep 6.

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