Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity

Mohebali, Donya; Matos, Jason; Chang, James D.

doi:10.1002/ehf2.12113

Cited by 11 publications

(9 citation statements)

References 13 publications

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“…Several of the canonical anti-cancer drugs assayed in this study showed greater toxicity against HeLa cells than did the NSAIDs. Although the IC 50 values were lower against 3T3 or HFF1 fibroblasts or MCF-10A breast epithelium cells, all of the chemotherapy drugs have shown significantly greater cardiotoxicity [ 42 , 66 , 67 , 68 , 69 ] than the NSAIDs which are presumably less harmful [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

et al. 2020

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This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC50 = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC50 doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

et al. 2020

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“…Notably, we found that specific concomitant intake of anticancer drugs on top of gemcitabine were more likely to be associated with different type of cardiotoxicities such as platins with MI, HER-2 blockers with HF, and immune checkpoint inhibitors with pericardial disorders. Indeed, these drugs are known to induce these conditions and the hypothesis of toxic synergy or multiple hit mechanisms with these combinations is likely [ 18 , 45 , 46 ]. Overall, the co-administration of drugs that can induce CV-ADR should strengthen the surveillance of high-risk cardiovascular patients receiving combination of such agents.…”

Section: Discussionmentioning

confidence: 99%

Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study

Hilmi

Éderhy²,

Waintraub

et al. 2020

Pharmaceuticals

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Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization’s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 01 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) ≥ 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.

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“…Few cases are reported in the literature about cardiac dysfunction caused by isolated treatment with gemcitabine [ 1 ]. Some cases reported cardiomyopathy induced by gemcitabine after treatment with cardiotoxic anticancer drugs such as anthracyclines [ 8 ]. Generally treatment with gemcitabine can cause supraventricular tachycardia including atrial fibrillation, especially after 18–24 h of infusion [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some cases reported cardiomyopathy induced by gemcitabine after treatment with cardiotoxic anticancer drugs such as anthracyclines [ 8 ]. Generally treatment with gemcitabine can cause supraventricular tachycardia including atrial fibrillation, especially after 18–24 h of infusion [ 8 ]. In addiction, several case reports have demonstrated acute myocardial infarction post-gemcitabine injection secondary to drug-induced vascular injury or endothelial damage [ 9 – 10 ].…”

Section: Discussionmentioning

confidence: 99%

Fatal Heart Failure Induced By Pazopanib In A Sarcoma Patient Previously Treated With Gemcitabine

Lisi¹,

Manno²,

Filorizzo³

et al. 2020

Journal of the Saudi Heart Association

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Gemcitabine is commonly used for various solid organ malignancies with rarely reported cardiac side effects such as cardiomyopathy. Pazopanib usually can cause arterial hypertension but cases of heart failure have recently been reported. We describe a case of fatal heart failure after treatment with gemcitabine and pazopanib in a 55-year-old female with sarcoma. Patient developed left ventricular dysfunction after gemcitabine treatment and acute heart failure after 22 days of pazopanib treatment which led to death. Physicians should be aware of the cardiotoxicity risk when managing the use of pazopanib especially in patients previously treated with other cardiotoxic drugs.

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Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity

Cited by 11 publications

References 13 publications

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study

Fatal Heart Failure Induced By Pazopanib In A Sarcoma Patient Previously Treated With Gemcitabine

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