Cardiovascular Toxicity of Antitumor Drugs: Dimension of the Problem in Adult Settings

Carver, Joseph R.; Desai, Chaitali J.

doi:10.1002/9780470660379.ch5

Cited by 5 publications

(1 citation statement)

References 290 publications

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“…Some well known and documented are the anthracyclines, alkylating agents, antimetabolites, tyrosine kinase inhibitors, and biologics such as trastuzumab to name a few. [1][2][3] Multiple myeloma (MM) is a plasma cell leukemia that results in immunosuppression, coagulopathies, and renal failure. Bacterial infection is the leading cause of death in people afflicted with MM.…”

Section: Introductionmentioning

confidence: 99%

Heart failure secondary to carfilzomib-induced heart block in multiple myeloma patients

Tjionas

Gupta

2016

J Oncol Pharm Pract

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Carfilzomib is a proteasome inhibitor and immunomodulator used to treat patients with multiple myeloma who have disease progression refractory to bortezomib. The difference in agents is that carfilzomib is an irreversible inhibitor of 20 s proteasome. The most common side effects of carfilzomib are fatigue, nausea, diarrhea, anemia, thrombocytopenia, dyspnea, and pyrexia. Less frequent side effects include cardiac manifestations for which we will explore with more detail. In this case report, we describe a 70-year-old female with multiple myeloma presenting to the emergency department with complaint of dyspnea. Patient was discovered to be in heart failure with atrioventricular block necessitating placement of a pacemaker.

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Section: Introductionmentioning

confidence: 99%

Heart failure secondary to carfilzomib-induced heart block in multiple myeloma patients

Tjionas

Gupta

2016

J Oncol Pharm Pract

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Naphthoquinoxaline metabolite of mitoxantrone is less cardiotoxic than the parent compound and it can be a more cardiosafe drug in anticancer therapy

et al. 2016

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Mitoxantrone (MTX) is an antineoplastic agent used to treat several types of cancers and on multiple sclerosis, which shows a high incidence of cardiotoxicity. Still, the underlying mechanisms of MTX cardiotoxicity are poorly understood and the potential toxicity of its metabolites scarcely investigated. Therefore, this work aimed to synthesize the MTX-naphthoquinoxaline metabolite (NAPHT) and to compare its cytotoxicity to the parent compound in 7-day differentiated H9c2 cells using pharmacological relevant concentrations (0.01-5 µM). MTX was more toxic in equivalent concentrations in all cytotoxicity tests performed [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, neutral red uptake, and lactate dehydrogenase release assays] and times tested (24 and 48 h). Both MTX and NAPHT significantly decreased mitochondrial membrane potential in 7-day differentiated H9c2 cells after a 12-h incubation. However, energetic pathways were affected in a different manner after MTX or NAPHT incubation. ATP increased and lactate levels decreased after a 24-h incubation with MTX, whereas for the same incubation time and concentrations, NAPHT did not cause any significant effect. The increased activity of ATP synthase seems responsible for MTX-induced increases in ATP levels, as oligomycin (an inhibitor of ATP synthase) abrogated this effect on 5 µM MTX-incubated cells. 3-Methyladenine (an autophagy inhibitor) was the only molecule to give a partial protection against the cytotoxicity produced by MTX or NAPHT. To the best of our knowledge, this was the first broad study on NAPHT cardiotoxicity, and it revealed that the parent drug, MTX, caused a higher disruption in the energetic pathways in a cardiac model in vitro, whereas autophagy is involved in the toxicity of both compounds. In conclusion, NAPHT is claimed to largely contribute to MTX-anticancer properties; therefore, this metabolite should be regarded as a good option for a safer anticancer therapy since it is less cardiotoxic than MTX.

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Can We Predict Clinical Cardiotoxicity with Cardiac Biomarkers in Patients After Haematopoietic Stem Cell Transplantation?

et al. 2014

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The long-term prognosis of patients after haematopoietic stem cell transplantation (HSCT) has greatly improved. Cardiac complications represent unresolved and potentially life-threatening conditions in these patients. We prospectively examined 37 consecutive patients with a median age of 28 years who underwent allogeneic HSCT. Biomarkers of cardiac injury were measured serially before the conditioning regimen, the first day after HSCT and then 14, 30, 90 and 180 days after HSCT. Echocardiography was performed before and 1 month after HSCT. Eleven patients (30%) had persistently increased NT-proBNP values, 14 patients (38%) had only transient elevations and 12 (32%) had no changes in NT-proBNP concentrations for a period exceeding 14 days after HSCT. Elevated NT-proBNP values at day 14 after HSCT remained an independent predictor of cardiotoxicity during the first 6 months after HSCT (P < 0.01). Patients with persistent elevations in NT-proBNP also had significant elevations in hs-cTnT concentrations (P < 0.01). Only patients with persistently increased NT-proBNP had a significant worsening in systolic and some diastolic echocardiographic parameters, and we observed in this group the highest values of both cardiomarkers during the 6-month period. Forty-five percent of these patients developed clinical manifestation of cardiotoxicity. Elevations in NT-proBNP concentrations at day 14 after HSCT can predict patients at risk of developing cardiac events during the first 6 months after HSCT. Simultaneous elevations of both cardiomarkers (NT-proBNP and hs-cTnT) persisting 14 days after HSCT had a sensitivity of 83% and a specificity of 80.69%.

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Cardiovascular Toxicity of Antitumor Drugs: Dimension of the Problem in Adult Settings

Cited by 5 publications

References 290 publications

Heart failure secondary to carfilzomib-induced heart block in multiple myeloma patients

Heart failure secondary to carfilzomib-induced heart block in multiple myeloma patients

Naphthoquinoxaline metabolite of mitoxantrone is less cardiotoxic than the parent compound and it can be a more cardiosafe drug in anticancer therapy

Can We Predict Clinical Cardiotoxicity with Cardiac Biomarkers in Patients After Haematopoietic Stem Cell Transplantation?

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