dexrazoxane / Generic mfg. - LARVOL DELTA

Molecular Insights into Doxorubicin-Induced Cardiotoxicity and Phytochemical-Based Cardioprotection: Challenges and Future Strategies. (PubMed, Drug Metab Rev) - "Although dexrazoxane is the only FDA-approved cardioprotective agent, concerns about its long-term safety and potential interference with doxorubicin's antitumor effectiveness have increased the search for safer alternatives. Despite promising preclinical evidence of their antioxidant, anti-inflammatory, and anti-apoptotic properties, the clinical use of phytochemicals is limited by issues such as low bioavailability, poor specificity, dose-dependent toxicity, variable pharmacokinetics, and lack of standardisation. Therefore, innovative approaches-such as ligand-targeted delivery systems, nanotechnology-based formulations, and structural modifications of lead compounds-are essential to enhance their pharmacological properties, safety, and therapeutic effectiveness for effective cardioprotection against doxorubicin-induced toxicity."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Oncology • AMPK • KEAP1 • SIRT1

Progression-Free Survival (PFS) and Toxicity with Nivolumab-AVD Compared to Brentuximab Vedotin-AVD in Pediatric Advanced Stage (AS) Classic Hodgkin Lymphoma (cHL), Results of SWOG S1826 (ASH 2023) - P3 | "Dexrazoxane was permitted, but not mandated. In early follow-up, N-AVD and BV-AVD are well tolerated and associated with low rates of irAEs in pts ages 12-17 y. With 12.1 mos median follow-up the PFS benefit observed for N-AVD in pediatric pts mirrors that observed in the overall study. RT usage is lower, and cumulative doxorubicin dose is higher than historical pediatric cHL trials. The difference in rate of discontinuation between study arms and by age group needs further evaluation."

Clinical • Metastases • Classical Hodgkin Lymphoma • Endocrine Disorders • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Inflammation • Lymphoma • Neutropenia • Oncology • Pediatrics • Pneumonia • Septic Shock

PROGRESSION-FREE SURVIVAL (PFS) WITH NIVOLUMAB-AVD IS SUPERIOR TO BRENTUXIMAB VEDOTIN-AVD WITH 2-YEAR FOLLOW-UP OF S1826 IN ADOLESCENT ADVANCED STAGE (AS) CLASSIC HODGKIN LYMPHOMA (CHL) (ISHL 2024) - P3 | "80% of adolescent pts received dexrazoxane. N-AVD is well tolerated in adolescents 12–17 y, with high PFS and EFS and minimal use of RT compared to prior pediatric HL studies. N-AVD is a new standard of care for adolescents with AS cHL."

Metastases • Endocrine Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Neutropenia • Oncology • Pain • Pediatrics • Septic Shock

AML16: A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=206 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Dexrazoxane Protects Against Hand-Foot Syndrome-Like Skin Damage in Pegylated Liposomal Doxorubicin-Treated Mice. (PubMed, J Toxicol) - "Although not significant, Topo IIα expression followed an analogous pattern to Topo IIβ expression. In conclusion, we demonstrated that DXZ inhibited PLD-induced skin damage."

Journal • Preclinical • Cardiovascular • Dermatology • Oncology

Mechanisms of Bellidifolin in Treating Doxorubicin-Induced Cardiotoxicity: Network Pharmacology, Molecular Docking, and Experimental Verification. (PubMed, Front Biosci (Landmark Ed)) - "BEL presents as a promising therapeutic candidate for cardiotoxicity, likely through its anti-fibrotic effects via the reduction of TGF-β1, α-SMA, Col I, and Col III expression, alongside regulation in the PI3K-AKT signaling pathway."

Journal • Cardiovascular • Fibrosis • Immunology • TGFB1

COMPARATIVE EFFECTIVENESS OF CONTINUOUS INFUSION, DEXRAZOXANE, EPIRUBICIN, AND LIPOSOMAL DOXORUBICIN FOR PREVENTION OF ANTHRACYCLINE CARDIOTOXICITY: A NETWORK META-ANALYSIS (ACC 2026) - "Abstract is embargoed at this time."

HEOR • Retrospective data • Cardiovascular

DEXRAZOXANE SIGNIFICANTLY REDUCES ANTHRACYCLINE-INDUCED CARDIAC DYSFUNCTION IN ADULT PATIENTS: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS (ACC 2026) - "Abstract is embargoed at this time."

Retrospective data • Review

Chemotherapy-Induced Cardiotoxicity: Mechanisms, Detection and Emerging Therapies in Cardio-Oncology. (PubMed, Discoveries (Craiova)) - "HER2-directed therapies, such as trastuzumab, interfere with cardioprotective ErbB signaling, typically producing reversible cardiac impairment. Preventive and management strategies incorporate cardioprotective agents like ACE inhibitors, β-blockers, dexrazoxane, and emerging therapies such as SGLT2 inhibitors. Modern cardio-oncology emphasizes a multidisciplinary, precision-based approach integrating early detection, genetic risk assessment, and targeted prophylaxis to preserve cardiac function while maintaining oncologic efficacy, thereby enhancing both survival and quality of life for cancer patients."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Metabolic Disorders • Oncology • ICOS

ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity. (PubMed, JACC Basic Transl Sci) - "This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell-derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy."

Journal • Cardiovascular • Oncology

Condensin II mediates resistance to genotoxic stress and prevents mitotic defects in Arabidopsis. (PubMed, Plant Physiol) - "The anaphase bridges were more frequent upon treatment with zebularine or ICRF-187 and the duration of mitosis was prolonged. Altogether, we demonstrate that proper large-scale chromatin organization by Condensin II is important for resistance to DNA damage in Arabidopsis."

Journal

AEWS1031: Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma (clinicaltrials.gov) - P3 | N=642 | Completed | Sponsor: Children's Oncology Group | Unknown status ➔ Completed

Trial completion • Trial completion date • Embryonal Tumor • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer. (PubMed, J Clin Oncol) - "Among young adult-aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Cardiotoxicity induced by traditional chemotherapy: mechanisms and mitigation strategies. (PubMed, Apoptosis) - "Clinical trials and case reports have demonstrated that patients with chemotherapy-induced cardiotoxicity may benefit from therapeutic interventions such as angiotensin-converting enzyme inhibitors, dexrazoxane, and β-blockers. However, limitations associated with these potential biomarkers and therapeutic agents warrant further discussion because of the lack of solid evidence from large-scale, prospective clinical studies. In summary, further research is imperative to enhance the understanding, monitoring, and therapeutic management of cardiotoxicity associated with traditional chemotherapeutic agents."

Biomarker • Journal • Review • Cardiovascular • Oncology • CRP • IL6 • MPO • TNFA

Dual protection by naringin and dexrazoxane against iron-induced erythrocyte damage: Exploring their synergistic regulation of ferroptosis and eryptosis. (PubMed, J Trace Elem Med Biol) - "These findings concluded that NAR is a potential alternative to traditional DEX as iron chelators. Moreover, NAR is a promising therapy for disorders connected with iron overloading."

Journal • Hematological Disorders • Pain • GPX4

Dexrazoxane Cardioprotection in pediatric ALL: a historical control cohort study. (PubMed, Cardiooncology) - "Incorporating a cardioprotective strategy into pediatric ALL treatment protocols appears to lower the risk of anthracycline-induced cardiotoxicity without compromising safety, hence boosting patient outcomes. These findings should be interpreted in light of the historically controlled, nonrandomized design and potential time-related confounding."

Journal • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Hesperetin's antigenotoxicity: the impact on EMS-made lesions within Drosophila melanogaster somatic cells' DNA, disclosed through molecular modeling. (PubMed, Phytomedicine) - "This dual-mode pharmacological profile positions Hes as a potential adjuvant in chemotherapy, capable of counteracting the mutagenic and carcinogenic consequences associated with alkylating agents."

Journal

Successful Treatment of Mediastinal Anthracycline Extravasation by Administration of Dexrazoxane. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal

RMS13: Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy (clinicaltrials.gov) - P2 | N=115 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor

Cardioprotection without risk? meta-analysis of prophylactic agents in low-risk cancer patients on anthracyclines (ASH 2025) - "We included randomized controlled trials (RCTs) of prophylactic ACE inhibitors, ARBs, beta-blockers, statins, dexrazoxane, or SGLT2 inhibitors in adults without pre-existing cardiovascular risk factors...Agents studied included beta-blockers (nebivolol, carvedilol, bisoprolol), ACE inhibitors (ramipril), ARBs (telmisartan), and spironolactone. Treatment duration ranged from 4 months to 1 year; anthracycline doses reached up to 689 mg/m² (epirubicin) or 536 mg/m² (doxorubicin)...The protective benefit was greater in contexts involving higher cumulative anthracycline doses and concurrent cardiotoxic therapies such as trastuzumab...However, high heterogeneity limits firm conclusions. Given the moderate effect size and heterogeneity, further large-scale, well-formulated trials are essential to identify optimal cardioprotective agents and precise patient selection criteria."

Retrospective data • Breast Cancer • Congestive Heart Failure • Heart Failure • Oncology • Solid Tumor

Subclinical cardiac changes following CPX-351 induction in adults with favorable/intermediate-risk AML (ASH 2025) - "If lesser toxicity is shown, CPX-351 could potentially be preferred in patients withpreexisting cardiac dysfunction or elevated risk for heart failure, and may reduce the need forcardioprotective agents such as dexrazoxane. As with any recently introduced agent that may be used toreplace standard therapy, it is crucial to fully characterize any toxicity profile, including with long-termfollow-up. We previously conducted a pilot study of CPX-351 with or without gemtuzumab ozogamicin(GO) in 25 adults (age 15%, including one who met both criteria. These five patients(20%) represent the subset with significant cardiac changes.In this cohort, both EF and GLS reductions were already evident post-induction in patients with significantcardiac changes."

Clinical • Acute Myelogenous Leukemia • Alopecia • Congestive Heart Failure • Heart Failure • Immunology • Myelodysplastic Syndrome

Early cardiotoxicity and survival in pediatric Acute Myeloid Leukemia: The mediating roles of relapse and salvage chemotherapy intensity (ASH 2025) - "Early cardiotoxicity may further affect OS by limiting the use of intensiveATC-based reinduction regimens at relapse leading to reduced post-relapse survival. The new era of nearuniversal use of dexrazoxane cardioprotection in pediatric AML therapy may present opportunities forintensification of reinduction regimens with ATC at relapse."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics

Initiation of ACE inhibitors or beta-blockers during frontline therapy for pediatric Acute Myeloid Leukemia and the impacts on cardiotoxicity incidence and survival outcomes: A target trial emulation (ASH 2025) - "The MSM incorporated inverse-probability-of-censoringweights to account for artificial censoring introduced by the aforementioned cloning procedure, adjustingfor both time-fixed (age, sex, race/ethnicity, cytomolecular risk, insurance, presentation acuity, trialenrollment, dexrazoxane use in induction I) and time-varying confounders (blood pressure, bacteremia,ICU-level requirements, empiric/definitive anti-infective use)...In contrast, ACEi showed no measurable benefit across anyof the evaluated outcomes. These results support further investigation into the role of BB as acardioprotective strategy during frontline chemotherapy, including evaluation of optimal initiation timingand the comparative effectiveness of different BB agents."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics

Optimization of induction chemotherapy in pediatric patients with Acute Myeloid Leukemia: Real-world evidence to support removal of etoposide from induction 1 (ASH 2025) - "Introduction: Induction chemotherapy for pediatric AML has historically used cytarabine, daunorubicinand etoposide (ADE)...This may be particularlytrue in the modern era in which therapeutic intensity can be achieved by adding gemtuzumab-ozogamycin (GO)...Relatedly, most patients treated onstudy for cycle 1, stayed on for cycle 2: ADE 84% and DA 94%.We conducted two sensitivity analyses: one limited to patients diagnosed after 2020 to account fortemporal differences in pediatric AML including expanded cytomolecular and improved MRD testing,enhanced supportive care (e.g. dexrazoxane) and additional salvage options, and one restricted topatients who received GO in induction 1... These real-world data convincingly demonstrate comparable outcomes with ADE and DAwhen used in induction 1, particularly in patients who receive GO. These data suggest that DA can besafely used as standard backbone chemotherapy for pediatric patients in this cycle, which may reduceetoposide-related..."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics

Real-world post-relapse survival outcomes in children with Acute Myeloid Leukemia by race and ethnicity (ASH 2025) - "We performed pairwise comparisonsbetween NHB and Hispanic patients against NHW patients (reference group) using chi-square andFisher's exact tests for frontline therapy characteristics (history of bacteremia/sepsis, CTCAE Grade ≥2cardiotoxicity, dexrazoxane receipt, hematopoietic stem cell transplant [HSCT] receipt in CR1, completionof frontline therapy) and clinical characteristics at relapse (early vs. late relapse, cytomolecular riskprofile, body mass index [BMI], acuity, Grade ≥2 cardiotoxicity measured by echocardiogram within 7days of relapse)... NHB children with AML experience greater than 50% increased hazard of death post-relapsecompared to NHW children, driven by poor outcomes after early relapse. This survival disparity occursdespite comparable rates of several major frontline therapy characteristics and overall rates of frontlinetherapy completion, suggesting that downstream intermediates are driving OS differences. Our dataindicate potential differences..."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Obesity • Septic Shock