Table 2.
Therapeutic approaches targeting oxidative stress and inflammation for the prevention of anthracycline (ANT)-related cardiotoxicity: evidence from preclinical studies and clinical trials
| Antioxidant agents | ||||
|---|---|---|---|---|
| First Author, year (ref.) | Molecule | Study design | Population | Main results |
| Macedo et al., 2019 [56] | Dexrazoxane | Meta-analysis | Patients with BC from 9 clinical trials (n = 2177) | Reduction in cardiac events and HF incidence; no effects on the efficacy of anticancer therapy |
| Akolkar et al., 2017 [61] | Vitamin C | In vitro study | Rat CMs | Inhibition of pro-oxidant and pro-inflammatory cascade |
| Akolkar et al., 2017 [62] | Vitamin C | Animal study | Rats receiving ANT | Inhibition of pro-oxidant and pro-inflammatory cascade, lower rates of cardiac damage, systolic and diastolic dysfunction |
| Berthiaume et al., 2005 [63] | Vitamin E | Animal study | Rats receiving ANT | No prevention of mitochondrial dysfunction and histological changes in the heart |
| Carbone et al., 2012 [64] | Omega 3 PUFA | Animal study | Sheep receiving ANT | Exacerbation of ANT cardiotoxicity |
| Iarussi et al., 1994 [68] | Coenzyme-Q | Clinical study (not RCT) | Patients with ALL (n = 20) | Reduction in LV systolic dysfunction and wall motion abnormalities |
| Chen et al., 2016 [69] | Coenzyme-Q | Animal study | Rats receiving ANT | Reduction in histological changes in the heart |
| Najafi et al., 2019 [70] | Melatonin | Systematic review of pre-clinical studies | 28 studies (mostly on mice/rats) | Decreased mortality, body weight and heart weight, ascites; reduction of histological changes in the heart |
| Myers et al., 1983 [71] | N-acetylcysteine | RCT | Patients with solid tumors (n = 54) | No difference in HF incidence |
| Waldner et al., 2006 [72] | L-carnitine | RCT | Patients with NHL (n = 40) | No difference in HF incidence |
| Gallegos-Castorena et al., 2007 [73] | Amifostine | Clinical study (not RCT) | Patients with osteosarcoma (n = 28) | No difference in HF incidence |
| Kheiri et al., 2018 [77] | Carvedilol | Meta-analysis | Patients with solid or blood cancer (n = 633) | Reduction in HF incidence and of absolute LVEF decrease |
| Bosch et al., 2013 [78] | Carvedilol/enalapril | RCT | Patients with blood cancer (n = 90) | Preservation of LV systolic function |
| Hiona et al., 2011 [81] | Enalapril | Animal study | Rats receiving ANT | Preservation of LV systolic function and mitochondrial respiratory efficacy |
| Anti-inflammatory agents | ||||
| Reference | Molecule | Study design | Population | Main results |
| Sheibani et al., 2020 [86] | Dapsone | Animal study | Rats receiving ANT | Reduction in cardiac levels of prooxidant and proinflammatory factors; preservation of cardiac function |
| Sheta et al., 2016 [83] | Metformin or sitagliptin | Animal study | Rats receiving ANT | Blunting of inflammatory pathways and preservation of cardiac function (+ + sitagliptin) |
| Peng et al., 2019 [84] | Teneligliptin | In vitro study | Rat and human CMs | Reduction in CM damage, apoptosis, and proinflammatory cytokines |
| Seicean et al., 2012 [87] | Statins | Retrospective study | Patients with BC (n = 628) | Reduction in HF incidence and cardiac mortality |
ALL acute lymphoblastic leukemia, BC breast cancer, CM cardiomyocyte, HF heart failure, IL-1 interleukin-1, LV left ventricle, LVEF left ventricular ejection fraction, NHL non-Hodgkin lymphoma, PUFA polyunsaturated fatty acids, RCT randomized clinical trial, TNFα tumor necrosis factor alpha