Detection of Cardiotoxicity Using Right Ventricular Free Wall Longitudinal Strain in Low Cardiovascular Risk Breast Cancer Patients Receiving Low-Dose Anthracycline Treatment.

Objective Breast cancer patients who receive chemotherapy may develop cancer therapy-related cardiovascular toxicity, particularly if they have pre-existing cardiovascular risk factors. Notably, right ventricle dysfunction may manifest before the left ventricle. Our study aims to compare conventional echocardiography with global longitudinal strain (GLS) in low cardiovascular risk patients on low-dose anthracycline, focusing on early cardiotoxicity detection. Additionally, we explore the predictive role of right ventricular free wall longitudinal strain (RVFWLS) in cardiotoxicity. Methods In a recent study, 28 women with low cardiovascular risk who underwent low-dose anthracycline chemotherapy for breast cancer were assessed for cardiac function using two-dimensional echocardiography and speckle-tracking echocardiography. The measurements included left ventricular ejection fraction (LVEF), right ventricular systolic function (RVS'), tricuspid annular plane systolic excursion (TAPSE), left ventricular global longitudinal strain (LVGLS), and RVFWLS. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new decrease in LVEF by 10% or below 53% and/or changes in LVGLS/RVFWLS by 15%. Results In our study, no significant changes were observed in the LVEF following chemotherapy treatment. The LVEF values remained stable, changing slightly from 63 ± 3.7 to 65.0 ± 3.4, with a t-test value of 1.790 and a p-value of 0.079. Similarly, the analysis found no significant changes in RVS' and TAPSE values following chemotherapy treatment. However, significant changes were observed in strain measurements. LVGLS decreased from -21.2 ± 2.1 to -18.6 ± 2.6 (t-test = -4.116; df = 54, p=0.001), and RVFWLS decreased from -25.2 ± 2.9 to -21.4 ± 4.4 (t-test = -3.82; df = 54, p=0.001). Notably, 35% of participants showed changes in RVFWLS greater than 15%, whereas LVGLS changed by less than 15%. This indicates that RVFWLS is more sensitive to the treatment compared to LVGLS. Conclusions The study results indicate that during the initial phases of chemotherapy treatment in low cardiovascular risk patients, early changes in strain measures reveal subclinical cardiotoxicity. This suggests that GLS measurements are more effective at detecting early signs of myocardial damage and potential deterioration in cardiac function than traditional echocardiographic parameters. Additionally, it is noteworthy that RVFWLS exhibits greater sensitivity to these changes, regardless of the chemotherapy dosage and regimen.

NOX66 as Monotherapy, and in Combination With Carboplatin, in Patients With Refractory Solid Tumors: Phase Ia/b Study.

BACKGROUND: Although oral and intravenous forms of idronoxil have been well tolerated, the safety of NOX66, with idronoxil formulated as a rectal suppository, is not known. This Phase Ia/b clinical study (protocol No. NOX66-001A), known as Chemotherapy Enhancement Program-1, is the first to assess NOX66 in patients with refractory solid tumors. OBJECTIVE: The study aimed to determine the safety profile of NOX66 both as a monotherapy and in combination with carboplatin, and to evaluate whether or not NOX66 has a meaningful anticancer effect when combined with carboplatin in this patient population. METHODS: Chemotherapy Enhancement Program-1 was a multicenter, open-label, nonrandomized, 2-dose cohort study of NOX66 as monotherapy (Phase Ia) and in combination with carboplatin (Phase Ib). Patients with refractory solid tumors who had stopped responding to standard treatments were eligible to participate. Twenty patients were screened and 19 enrolled in the study. They were divided into 2 groups: cohort 1 (n = 8) received 1 suppository daily (400 mg) and cohort 2 (n = 11) received 2 suppositories daily (800 mg) for 14 consecutive days followed by 7 days of rest. Patients who completed Phase Ia without significant toxicity continued to Phase Ib, where NOX66 was combined with carboplatin for up to 6x 28-day treatment cycles, with low-dose carboplatin (600 mg) for cycles 1B through 3B and standard dose carboplatin (900 mg) for cycles 4B through 6B. The main outcomes assessed were safety (n = 18) and efficacy signals (n = 14). RESULTS: NOX66 generally was well tolerated at 400 mg and 800 mg, both as monotherapy and in combination with carboplatin in patients with refractory solid tumors. The safety profile was consistent for oncology patients, with 77.8% experiencing at least 1 treatment-emergent adverse event. The most common adverse events were blood and lymphatic system disorders (44.4%), with only anemia considered as possibly related to NOX66. Although the study was primarily designed to assess safety and tolerability, the efficacy measurements demonstrated that most patients had stable disease or better by study end. CONCLUSIONS: The favorable safety profile of NOX66 provides reassurance to justify continuation of clinical research. The efficacy findings are encouraging in terms of the chemosensitizing potential of NOX66 in refractory solid tumors. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).