Dexrazoxane 500mg powder and solvent for solution for infusion vials

BackgroundThis meta-analysis and systematic review aim to consolidate evidence on cardiotoxicity prevention and treatment strategies in patients receiving anthracyclines or HER2 receptor inhibitors, vital treatments for breast cancer and hematologic malignancies. By synthesizing existing research, the goal is to provide impactful insights that enhance patient care and outcomes.MethodsComprehensive research across PubMed, Scopus, EMBASE, and the Cochrane Central Register for Controlled Trials was conducted, selecting clinical trials focusing on cardioprotection in anthracyclines or HER2 inhibitor-treated individuals. Effect sizes were computed using OpenMeta (Analyst), with leave-out meta-analysis to assess potential small study effects. Meta-regression explored treatment duration and sample size effects. Evidence quality for primary outcomes was evaluated using ROB, Robins 2, and Newcastle-Ottawa tools.ResultsTwenty -three studies involving a total of 14,652 patients (13,221 adults and 1431 kids) were included in the current systematic review and meta-analysis. The risk of bias and methodological quality of the included studies suggested good and moderate quality. Patients prescribed β-blockers demonstrated a 74% lower likelihood of exhibiting cardiotoxicity symptoms (OR 1.736). Similarly, the use of dexrazoxane was linked to a threefold decrease in cardiac abnormalities risk (OR 2.989), and ACE inhibitor administration showed half the risk compared with the control group (OR 1.956).ConclusionsThrough this systematic review and meta-analysis, it was shown that there is a reduction in cardiotoxicity from either anthracyclines or HER2 inhibitors in patients receiving pharmacoprophylaxis.

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Advances in the field of oncology have led to the advent of doxorubicin (DOX), an anthracycline chemotherapeutic agent, through which cancer survival rates have remarkably improved. There has, however, been a rise in adverse effects from the use of DOX, most notably cardiotoxicity. DOX-induced cardiotoxicity is thought to arise through the generation of reactive oxygen species (ROS), causing mitochondrial dysfunction in the cardiomyocytes. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and focused on cancer patients undergoing DOX therapy. The research question addressed interventions aimed at preventing DOX-induced cardiotoxicity. Google Scholar, PubMed, and ScienceDirect databases were used to conduct a systematic search. Next, screening was carried out by reviewing the title and abstract of various articles to exclude irrelevant studies, followed by the retrieval of full-text articles. Scale for the assessment of narrative review articles 2 (SANRA 2) for narrative reviews, a measurement tool to assess systematic reviews (AMSTAR) checklist for systematic reviews, and the Cochrane risk of bias tool for randomized controlled trials (RCTs) were the tools employed for quality assessment. This systematic review provides convincing evidence about preventive interventions to counteract DOX-induced cardiotoxicity. Primary prevention strategies against DOX-induced cardiotoxicity include pharmacological and non-pharmacological measures. Dexrazoxane reduces cardiotoxicity without therapeutic compromise. Beta-blockers showed mixed results in preserving cardiac function. The research on renin-angiotensin-aldosterone system (RAAS) inhibitors suggests that most of these agents can reduce the risk of DOX-induced cardiotoxicity. The liposomal formulation of DOX decreases cardiotoxicity without sacrificing effectiveness. Chemotherapy regimens should be supplemented with cardioprotective medications to increase therapeutic efficacy and lower cardiac risks. Exercise is an essential non-pharmacological strategy for decreasing DOX-induced cardiotoxicity. It acts by lowering oxidative stress, maintaining mitochondrial function, and averting apoptosis. Other non-pharmacological interventions through antioxidative, anti-apoptotic, and mitochondrial protective mechanisms, such as resveratrol, vitamin E, curcumin, and visnagin, show promise in lowering DOX-induced cardiotoxicity and may be useful as supplementary therapy during cancer treatment. In conclusion, this review highlights the need for a multimodal strategy that incorporates different tactics, as well as the need for additional research and strong clinical trials, with the ultimate goal of protecting cardiac health in patients receiving chemotherapy with DOX.

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PurposeThis study aimed to systematically assess the efficacy of cardioprotective agents in preventing anthracycline-induced cardiotoxicity in patients with breast cancer using a comprehensive network meta-analysis (NMA).MethodsThis study included patients with breast cancer undergoing anthracycline-based chemotherapy. Randomized controlled trials (RCTs) published before March 2020 were identified through systematic searches in MEDLINE, Cochrane CENTRAL, Web of Science, and CINAHL. The primary outcome was left ventricular ejection fraction (LVEF), assessed using cardiac magnetic resonance imaging, multigated radionuclide angiography, or echocardiography. The NMA integrated direct and indirect comparisons to estimate the relative effectiveness of pharmacological interventions.ResultsThe systematic review included 31 RCTs with 3,228 participants, whereas the NMA synthesized 25 effect sizes from 15 RCTs. Mineralocorticoid receptor antagonists (MRAs) [standardized mean difference (SMD): -1.78, 95% confidence interval (CI): -2.81 to -0.75] and trimetazidine (SMD: -1.12, 95%CI: -2.32 to -0.09) exhibited the most substantial cardioprotective effects. Dexrazoxane (SMD: -0.53, 95%CI: -1.90 to -0.02) and β-blockers (SMD: -0.34, 95%CI: -0.70 to 0.02) showed potential benefits, albeit with greater uncertainty. Direct comparisons showed that dexrazoxane was more effective than β-blockers (SMD: -1.25, 95%CI: -2.22 to -0.48), with mineralocorticoid receptor antagonists (MRAs) outperforming both. Despite heterogeneity and potential publication bias, mineralocorticoid receptor antagonists (MRAs) and trimetazidine consistently ranked as the most effective interventions. LVEF findings confirmed the cardioprotective benefits of β-blockers, ARBs, ACE inhibitors, and dexrazoxane.ConclusionsRCT evidence suggested that cardioprotective drugs effectively mitigate anthracycline-induced LVEF decline. However, the lack of direct head-to-head trials limits definitive conclusions on comparative efficacy, warranting trials in patients with lower baseline LVEF to optimize cardioprotective strategies.

Abstract licence: CC BY