dexrazoxane

P2, N=42, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2026 --> Mar 2026

Translational advances include established cardioprotective approaches such as dexrazoxane and liposomal formulations, alongside investigational strategies-including SGLT2 inhibitors, OCT3 blockade, and RARG agonists-that require prospective validation. Complementary efforts to overcome resistance encompass nanomedicine-based delivery, STAT3 inhibition, and RNA-directed therapeutics. By converging molecular mechanisms, pharmacogenomic insights, and biomarker discovery, this review outlines precision strategies to sustain doxorubicin benefit while minimizing cardiovascular harm.

P2, N=65, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Oct 2026 --> Oct 2027

P=N/A, N=420, Recruiting, Children's Oncology Group | Trial completion date: Dec 2025 --> Dec 2026

P3, N=236, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

These strategies highlight recent data supporting the emerging cardioprotective role of exercise training, as well as the use of SGLT2 inhibitors, ACE inhibitors, angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, statins and dexrazoxane. We present a comprehensive synthesis emphasizing the critical role of cardio-oncology in identifying patients at high risk, understanding clinical outcomes, and implementing practical, evidence-based strategies. Our findings underscore the need for proactive cardiovascular risk management to enhance long-term care in oncology patients.

DSS confers cardioprotection against DOX-induced injury by disrupting the vicious circle formed by ROS and JNK, which mediated impairment of mitochondrial quality control, attenuating oxidative stress, and reducing apoptosis. These findings highlight DSS as a promising therapeutic candidate for mitigating chemotherapy-associated cardiotoxicity.

P1, N=30, Recruiting, Andrew E. Place, MD | Active, not recruiting --> Recruiting | N=13 --> 30 | Trial completion date: Jul 2028 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

Phytochemicals derived from Mentha arvensis demonstrate potential as dual-action agents capable of mitigating doxorubicininduced cardiotoxicity while preserving anticancer activity. However, when used alone, these compounds exhibited only moderate therapeutic potential. Combinatorial strategies involving Dexa may enhance cardioprotective efficacy while reducing associated limitations, possibly through modulation of ferroptosis-related pathways. Nevertheless, rigorous experimental validation remains essential. Future studies should employ well-established in vivo oncogenic cardiotoxicity models incorporating Dox, Dexa, and phytochemicals concurrently to elucidate shared molecular targets and confirm therapeutic efficacy against both cancer and DIC.

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.

P2, N=206, Active, not recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Jun 2025 --> Sep 2025

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.