Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity

Chang, Vivian Y.; Wang, Jessica

doi:10.1007/s11912-018-0696-8

Cited by 52 publications

(37 citation statements)

References 69 publications

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“…7,[9][10][11][12] Through a linkage of clinical trial data and administrative data resources, we plan to evaluate the utility of cardiac-directed interventions on the progression and potential resolution of cardiac dysfunction. Finally, additional work is ongoing to discover and validate germline genetic variants that may predispose to anthracycline-associated cardiotoxicity and influence treatment efficacy through drug metabolism or other pharmacogenomics pathways, [27][28][29][30][31] as well as to investigate the increased risk of cardiotoxicity in black patients. A more complete understanding of the development of cardiotoxicity and effective interventions will inform evidence-based strategies to improve both the cardiovascular and oncologic outcomes for children with cancer.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

Getz

Sung

et al. 2019

JCO

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Purpose Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). Methods Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. Results Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). Conclusion Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

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Section: Discussionmentioning

confidence: 99%

Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

Getz

Sung

et al. 2019

JCO

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“…For example, initiation of statin therapy for patients with elevated calcium scores on chest CT scans, which are routinely done as part of cancer staging, can be c o n s i d e r e d f o r p r e v e n t i o n o f c o r o n a r y e v e n t s . Pharmacogenetic testing for susceptibility to anthracyclineinduced cardiotoxicity that is already recommended in children with cancer can also be studied in adult cancer patients in an effort to identify those who are most vulnerable [95]. While the agent dexrazoxane has been studied in the pediatric and advanced breast cancer population with demonstrated cardioprotective effects [96,97], its use and efficacy in the adult hematologic population is less clear.…”

Section: Future Avenues and Strategiesmentioning

confidence: 99%

Cardiac Complications in the Adult Bone Marrow Transplant Patient

et al. 2019

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Purpose of Review Due to advancements in oncologic treatment strategies and techniques, the number of survivors who have undergone hematopoetic stem cell transplant (HCT) continues to increase in the United States; this number is projected to reach 502,000 by the year 2030. There is significant interest within the field of cardio-oncology to identify cardiotoxicity and cardiovascular disease in the HCT population. Epidemiologic studies analyzing both short-and long-term cardiovascular effects, risk stratification modeling, cardioprotective strategies, and expert consensus documents for cardiotoxicity surveillance recommendations are reviewed. Recent Findings Patients who have undergone HCT are at increased risk of cardiovascular events and mortality compared to matched controls. The type of cardiotoxicity and the incidence rates vary based on specific therapeutic regimens and pre-existing cardiovascular risk factors. Life-threatening cardiotoxicity can present during HCT as acute heart failure, arrhythmias, pericardial tamponade, or cardiac arrest; or it can present late after treatment as cardiomyopathy, ischemic heart disease, vascular disease, stroke, or comorbid conditions, such as hypertension and diabetes mellitus that are associated with cardiac events. Summary HCT is associated with excess cardiovascular risk partially due to exposure to cardiotoxic chemotherapy and radiation, as well as indirect and direct detrimental effects on cardiovascular reserve. This review discusses the epidemiology and the known cardiotoxic effects of historical chemoradiation agents in addition to newer targeted therapies. Recent expert consensus statements from cardiology and hematology/oncology societies are reviewed in regard to risk stratification of the cancer patient based on the type of treatments. Finally, gaps in knowledge are identified with proposed avenues of research that will allow for more accurate risk assessment, prediction, and potential treatment of the HCT patient in attenuating the risk of developing both short-and long-term cardiovascular comorbidities.

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“…However, their uses are limited due to multiple off-target toxicities, leading not only to a severe impact on the quality of life of patients but also to a reduction of doses or the selection of alternative therapies. One of the heaviest secondary effects observed in the case of doxorubicin treatment is strong cardiotoxicity [94,95]. Cisplatin is sometimes associated with ototoxicity, neurotoxicity, nephrotoxicity, myelosuppression, and nausea/emesis, especially for older patients [96].…”

Section: Chemotherapy Used As Single Agentmentioning

confidence: 99%

Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Gheysen

Saussez

Journé

2020

Cells

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Accounting for about 2% of cancers diagnosed worldwide, thyroid cancer has caused about 41,000 deaths in 2018. Despite significant progresses made in recent decades in the treatment of thyroid cancer, many resistances to current monotherapies are observed. In our complete review, we report all treatments that were tested in combination against thyroid cancer. Many preclinical studies investigating the effects of inhibitors of the MAPK and PI3K pathways highlighted the importance of mutations in such signaling pathways and their impacts on the subsequent efficacy of targeted therapies, thus reinforcing the need of more personalized therapeutic strategies. Our review also points out the multiple possibilities of combinatory strategies, particularly using therapies targeting proliferation, survival, angiogenesis, and in combination with conventional treatments such as chemotherapies. In any case, resistances to anticancer therapies always develop through the activation of alternative signaling pathways. Combinatory treatments aim to blockade such mechanisms, which are gradually decrypted, thus offering new perspectives for the future. The preclinical and clinical aspects of our review allow us to have a global opinion of the different therapeutic options currently evaluated in combination and to be aware about new perspectives of treatment of thyroid cancer.

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Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity

Cited by 52 publications

References 69 publications

Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

Cardiac Complications in the Adult Bone Marrow Transplant Patient

Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

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