Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study.

Forni, M; Malet‐Martino, Myriam; Jaillais, P; Shubinski, R; Bachaud, J.M.; Lemaire, Laurent; Canal, Pierre; Chevreau, Christine; Carrié, D; Soulié, P

doi:10.1200/jco.1992.10.11.1795

Cited by 301 publications

(226 citation statements)

References 21 publications

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“…Patients were treated according to CTX schemes containing 5-FU or capecitabine. The number of patients included in this analysis is comparable to that in the scarce, previously published reports [8,9].…”

Section: Discussionsupporting

confidence: 72%

“…The number of included patients is relatively small but similar to previously published papers related to cardiovascular aspects of 5-FU therapy [8,9]. Regrettably, novel echocardiography tools such as three-dimensional imaging could be used only in selected patients due to the modest availability of advanced ultrasound systems and were therefore not included in the analysis.…”

Section: Limitations Of the Studymentioning

confidence: 79%

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Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

et al. 2017

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A b s t r a c tBackground: Colorectal cancer (CRC) is the second most common cancer in women and the third in men in Poland. The role of chemotherapy (CTX) depends on the stage of CRC: adjuvant CTX is a standard treatment in stage III and should also be considered in stage II with risk factors. Aim:The aim of the paper was to assess the cardiovascular consequences of CTX in CRC enrolled to the ONCOECHO multicentre study (2012)(2013)(2014). To identify potential cardiotoxicity, we focused on myocardial function, heart rhythm and conduction disorders, and adverse cardiovascular events.Methods: Twenty-five CRC patients (12 women, mean age 61.3 years), all receiving six-month adjuvant CTX were included. Thirteen patients received 5-fluorouracil (5FU)-based CTX, and 12 patients received a capecitabine-based scheme. Subjects were assessed at baseline and followed-up three, six, and 12 months after the onset of treatment. In this analysis we focused on conduction abnormalities, systolic and diastolic function of the left ventricle (LV), and cardiovascular events. Results:In 12-month follow-up a decrease of selected tissue Doppler parameters (e.g. S'IVS, S'lat, and E'sept) was observed, and it was significant. LV structural parameters and ejection fraction (EF) remained unaffected. Changes in myocardial performance were not influenced by CTX regimen or treatment with beta-blockers or angiotensin-converting enzyme inhibitors. CTX did not affect LV structural parameters, EF, or conduction system, nor was it associated with cardiovascular events during the 12-month follow-up.Conclusions: CTX in CRC patients does not affect LV structural parameters and EF. It may, however, trigger subtle changes in myocardial performance detectable by tissue Doppler echocardiography after 12 months. Moreover, it causes a transient increase of QT, which resolves after CTX cessation.

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Section: Discussionsupporting

confidence: 72%

Section: Limitations Of the Studymentioning

confidence: 79%

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

et al. 2017

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“…half of the maximum tested dose, in the experiments investigating the suppressive effect of 5-FU combined with calcium supplementation. The fact that calcium supplementation managed to enhance the antitumor effect of 5-FU indicates that the combined treatment may represent a means of allowing the required therapeutic doses of 5-FU to be reduced (18).…”

Section: Discussionmentioning

confidence: 99%

Synergistically Anti-metastatic Effect of 5-Flourouracil on Colorectal Cancer Cells via Calcium-mediated Focal Adhesion Kinase Proteolysis

Park

Sundaramoorthy

Sim

et al. 2017

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Abstract. Aim: To investigate the possibility of enhancing an anti-metastatic effect of 5-fluorouracil (5-FU) on colorectal cancer (CRC) cells by combining it with continuous calcium supplementation. Materials and Methods: Optimal doses of 5-FU with/without lactate salt (CaLa) were determined via clonogenicity and 3- (4,5-dimethylthiazol-2-yl Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancerrelated death in both men and women (1). According to the estimates of the Global Cancer Control (GLOBOCAN) project, nearly 1.4 million people worldwide were diagnosed with CRC in 2012, with the Republic of Korea displaying the highest incidence rates, followed by Slovakia and Hungary (2).CRC that has grown into the wall can penetrate blood or lymph vessels; typically, cancer cells first invade nearby lymph nodes, and then spread to other parts of the body, such as the liver or lung (1, 3). Approximately 150,000 new cases are diagnosed each year, with about 20% of them already displaying metastases (2). Metastatic CRC is often harder to treat and tends to have a poor treatment outcome. As a result, patients with metastatic CRC have a low 5-year survival rate of about 11% (1, 2).In patients newly diagnosed with CRC, 5-fluorouracil (5-FU) is usually administered intravenously in combination with a second drug called leucovorin (4). Moreover, most patients with newly-diagnosed metastatic CRC undergo surgery after receiving chemotherapy with 5-FU (5). Other combinatorial treatments have also been tested for first-line chemotherapy of metastatic CRC, where a targeted drug, such as bevacizumab or cetuximab, is co-administered to increase the efficiency of 5-FU (6). However, these regimens suffer from increased toxicity, and cause symptoms such as neutropenia, severe diarrhea, and vomiting (7). Moreover, 5-FU is not an effective treatment strategy because it only delays micrometastasis. The mechanism through which 5-FU acts on CRC metastases remains unclear (8).Focal adhesion kinase (FAK), a protein kinase involved in cellular adhesion, is activated in several types of advancedstage cancer. In CRC cells, phosphorylation of FAK occurs on multiple residues, and overexpression of FAK has been detected in liver metastases of CRC (9). FAK has been implicated in the regulation of the expression of genes 103 Τhis article is freely accessible online.

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“…The reported incidence of cardiotoxicity related to 5-FU ranges from 1.2% to 18% [1,2,[12][13][14]. This wide variation is believed to be related to dose dependency as well as the frequency of drug administration.…”

Section: Epidemiologymentioning

confidence: 99%

5-fluorouracil induced cardiotoxicity: Review of the literature

Sorrentino

Kim²,

Foderaro³

et al. 2012

Cardiol J

175

138

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Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study.

Abstract: In our study, the incidence of high-dose 5FU-CVI cardiotoxicity was 7.6%. The hypothesis of a toxic cardiomyopathic process requires further confirmation.

Cited by 301 publications

References 21 publications

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

Synergistically Anti-metastatic Effect of 5-Flourouracil on Colorectal Cancer Cells via Calcium-mediated Focal Adhesion Kinase Proteolysis

5-fluorouracil induced cardiotoxicity: Review of the literature

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