QT Interval Prolongation Associated With Cytotoxic and Targeted Cancer Therapeutics

Chandrasekhar, Sanjay; Fradley, Michael G.

doi:10.1007/s11864-019-0657-y

Cited by 28 publications

(20 citation statements)

References 148 publications

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“…However, such events are not as obvious as other commonly encountered adverse events with these drugs like neutropenia, thrombocytopenia, anemia, fatigue, diarrhea and elevated liver enzymes. 29 , 30 …”

Section: Discussionmentioning

confidence: 99%

Thromboembolic Events in Patients with HER2-Negative, Hormone Receptor-Positive, Metastatic Breast Cancer Treated with Ribociclib Combined with Letrozole or Fulvestrant: A Real-World Data

Abdel‐Razeq

Sharaf

AlMasri

et al. 2022

CMAR

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Purpose Cyclin dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) modulate endocrine resistance and are integral treatment for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue in patients treated on clinical trials utilizing these agents. However, conflicting data started to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we report our experience on TEE in patients treated with one of these agents (ribociclib) in real-world settings. Patients and Methods All consecutive patients with metastatic breast cancer (mBC) treated with ribociclib combined with letrozole or fulvestrant were retrospectively reviewed. All episodes of radiologically confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib-related if diagnosed while patients are on the drug, or within 4 weeks after the last dose. Results A total of 305 patients, median age (range), 49 (22–87) years were enrolled. All patients had metastatic disease, and most (n=241, 79.0%) were with visceral metastasis. Ribociclib was used for a median duration of 7 months (range: 1–45) and was used beyond the first-line setting in 110 (35.9%) patients. TEE were confirmed on 6 (1.97%) patients; 3 were pulmonary embolism, 2 cerebral venous sinus thrombosis (CVST), and one case of limb ischemia and all were symptomatic. Similar rates of TEE were noted prior to initiation, and after stopping ribociclib. Conclusion In real-world settings, breast cancer patients treated with ribociclib, combined with aromatase inhibitors or fulvestrant, may not be at higher risk for thromboembolic events. However, unusual sites of thrombosis, like CVST, may raise some concerns.

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Section: Discussionmentioning

confidence: 99%

Thromboembolic Events in Patients with HER2-Negative, Hormone Receptor-Positive, Metastatic Breast Cancer Treated with Ribociclib Combined with Letrozole or Fulvestrant: A Real-World Data

Abdel‐Razeq

Sharaf

AlMasri

et al. 2022

CMAR

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“…Prolongation of the QTc interval is one of the known but relatively rare side effects of many anticancer drugs including several molecular targeted drugs (including sorafenib, crizotinib and nilotinib) and antihormonal drug (toremifene). These anticancer therapies have properties known to induce QTc interval prolongation through various mechanisms, including direct effects on ion channels and indirectly via intracellular signaling pathways (Chandrasekhar and Fradley, 2019). Fluoroquinolones and domperidone are commonly used to treat cancer patients with infections, nausea or vomiting.…”

Section: Discussionmentioning

confidence: 99%

Potentially Hazardous Drug-Drug Interactions Associated With Oral Antineoplastic Agents Prescribed in Chinese Tertiary Care Teaching Hospital Settings: A Multicenter Cross-Sectional Study

et al. 2022

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Background: Oral administration increases the risk of interactions, because most oral antineoplastic agents (OAAs) are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Potential drug–drug interactions (DDIs) are commonly observed in patients with cancer, while the extent to which OAAs related hazardous DDIs remains unclear.Methods: We studied the contraindication patterns between oral antineoplastic agents and other medications among cancer patients in two tertiary care teaching hospitals in China. A total of 20 clinically significant hazardous DDI pairs that involved 30 OAAs were identified based on the predetermined criteria. Patient medications were checked for DDIs by using the US Food and Drug Administration approved labeling. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out.Results: In this study, 13,917 patients were included and a total of 297 DDIs were identified. The results revealed that proton pump inhibitors (PPIs), dexamethasone and fluoroquinolones were the most often involved hazardous DDIs with OAAs. The most prevalent contraindication is the simultaneous use of certain molecular targeted agents and PPIs. In the result of the multivariate analysis, younger age (0–20 group), increasing number of drugs and patient treated with targeted therapy had a higher risk for DDIs.Conclusion: The prevalence of OAAs related hazardous DDIs appears to be low in the cancer patients. However, physicians and clinical pharmacologists should be aware of the potential hazardous DDIs when prescribing OAAs, especially certain pH-dependent molecular targeted agents and potential QTc prolonging drugs.

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“…There are several other similarities between COVID-19 and cardio-oncology that allow for trainee education with several examples being risk for QT prolongation, venous thromboembolism (VTE), and cytokine storm. Similar to how tyrosine kinase inhibitors and other chemotherapeutic agents can prolong the QT interval, so too can the proposed treatment regimens for COVID-19 for example hydroxychloroquine, azithromycin, and lopinavir-ritonavir [ 28 , 29 ]. Therefore, an important lesson to trainees caring for these patients is accurate QT interval assessment, measures to mitigate QT prolongation, and when to discontinue therapy to avoid putting patients at risk for ventricular arrhythmia and sudden cardiac death.…”

Section: Inpatient Clinical Experiencementioning

confidence: 99%

Cardio-oncology Training in the COVID-19 Era

Feldman

Liu

Steingart

et al. 2021

Curr. Treat. Options in Oncol.

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Opinion Statement Cardio-oncology is a field dedicated to the prevention, diagnosis, and management of cardiovascular disease in cancer patients before, during, and after cancer therapy. It is an emerging field with limited opportunities for structured education and training. In the year 2021, we cannot define the requirements of cardio-oncology training without acknowledging the impact of the global coronavirus disease 19 (COVID-19) pandemic. While this pandemic poses significant health risks to patients with cancer and cardiovascular disease as well as the providers who care for them, it also allows novel opportunities for the nascent field of cardio-oncology to readily adapt. In this article, we detail how the COVID-19 pandemic has impacted all aspects of cardio-oncology training, how programs and trainees can adapt to these challenges, and how lessons learned from the COVID-19 era can continue to positively impact cardio-oncology training for the foreseeable future.

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QT Interval Prolongation Associated With Cytotoxic and Targeted Cancer Therapeutics

Cited by 28 publications

References 148 publications

Thromboembolic Events in Patients with HER2-Negative, Hormone Receptor-Positive, Metastatic Breast Cancer Treated with Ribociclib Combined with Letrozole or Fulvestrant: A Real-World Data

Thromboembolic Events in Patients with HER2-Negative, Hormone Receptor-Positive, Metastatic Breast Cancer Treated with Ribociclib Combined with Letrozole or Fulvestrant: A Real-World Data

Potentially Hazardous Drug-Drug Interactions Associated With Oral Antineoplastic Agents Prescribed in Chinese Tertiary Care Teaching Hospital Settings: A Multicenter Cross-Sectional Study

Cardio-oncology Training in the COVID-19 Era

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