Cardiac Toxicity of 5-Fluorouracil: A Study on 1083 Patients

Labianca, Roberto; Beretta, G; Clerici, M.; Fraschini, Paolo; Luporini, G

doi:10.1177/030089168206800609

Cited by 275 publications

(171 citation statements)

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“…It is therefore reasonable to assume that this patient had 5-FU-induced cardiotoxicity as well as ischaemic heart disease. Patients with a history of coronary heart disease are more likely to experience 5-FU cardiotoxicity (Labianca et al, 1982). It may be for this reason that our patient had toxicity when receiving bolus (low dose) and infusional (high dose) 5-FU.…”

Section: Discussionmentioning

confidence: 91%

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Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity

Köhne

Thuss-Patience²,

Friedrich³

et al. 1998

Br J Cancer

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Summary Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.Keywords: 5-fluorouracil; cardiotoxicity; raltitrexed; colorectal neoplasms 5-Fluorouracil (5-FU)-associated cardiotoxicity was recognized 18 years after its first clinical use, after symptoms of chest pain typical of angina pectoris, in patients treated with 5-FU (Dent and McColl, 1965). Estimates of its incidence have been given with a range of 1.6% in larger series (Labianca et al, 1982) and up to 10% in smaller cohorts (Collins and Weiden, 1987). 5-FU should be discontinued in the case of cardiotoxicity to avoid the development of serious or fatal cardiac damage (Anand, 1994). However, the arsenal of effective antineoplastic compounds for the treatment of colorectal cancer is limited, and the identification of a drug that may be safely given to patients with cardiac toxicity after 5-FU administration is important. Here, we report the successful administration of raltitrexed (Zeneca, Macclesfield, Cheshire, UK), a new specific thymidylate synthase inhibitor, in two patients with 5-FU-induced cardiotoxicity. PATIENTS AND METHODS Case 1A 58-year-old female without any history of cardiovascular disease presented at our institution with lung and liver metastases of a sigmoid adenocarcinoma. She had received three cycles of weekly folinic acid 500 mg m-2 as a 2-h infusion and 5-FU 500 mg m-2 as an i.v. bolus in the middle of the folinic acid infusion repeated for 6 weeks followed by a 2-week rest period. This therapy was tolerated well without any cardiac toxicity. When the tumour progressed, treatment with high-dose 5-FU 2600 mg m-2 given as a weekly 24-h infusion plus folinic acid 500 mg m-2 as a 2-h infusion before 5-FU was initiated. Approximately 22 h after the start of the 5-FU infusion the patient complained of dyspnoea and retrosternal pain and the 5-FU infusion was stopped. The blood pressure was 80/60 mmHg and the heart rate was regular with 100 beats per min. The ECG obtained after onset of symptoms revealed non-specific ST segment elevation in the anterior and posterior leads with a normalization after 24 h (Figures 1 and 2). Serial measurements of serum cardiac enzymes were normal. One week later, the patient was given the same 5-FU/folinic acid regimen and also received isosorbide dinitrate, molsidomine and acetylsalicylic acid. Approximately 10 h after the start of the 5-FU infusion, the patient complained of dyspnoea and retrosternal chest pain. The ECG revealed temporary changes similar to those observed a week earlier. Again, serial determination of serum cardiac enzyme levels remained unchanged. An echocardiogram was normal except for a localized apical hypokinesia. The global ejection fraction w...

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Section: Discussionmentioning

confidence: 91%

“…Estimates of its incidence have been given with a range of 1.6% in larger series (Labianca et al, 1982) and up to 10% in smaller cohorts (Collins and Weiden, 1987). 5-FU should be discontinued in the case of cardiotoxicity to avoid the development of serious or fatal cardiac damage (Anand, 1994).…”

mentioning

confidence: 99%

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity

Köhne

Thuss-Patience²,

Friedrich³

et al. 1998

Br J Cancer

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“…Ischemia can occur in patients without underlying coronary artery disease (CAD) (incidence, 1.1%), but the incidence is higher in patients with CAD (4.5%). 22 Capecitabine is currently used in the treatment of breast and gastrointestinal cancers and is believed to be less toxic than 5-FU. Other reported cardiotoxic effects associated with capecitabine include angina or MI, 23 arrhythmias, ECG changes, and cardiomyopathy.…”

Section: Antimetabolitesmentioning

confidence: 99%

Cardiovascular Complications of Cancer Therapy

et al. 2004

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Abstract-The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various malignancies. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the demographics of the patient. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. In this article we review commonly used chemotherapy agents, including several recently approved medications, for their propensity to cause cardiotoxicity. Further research will be required to more accurately predict which patients are at risk for developing cardiotoxicity. In addition, management plans, as well as strategies to reduce cardiotoxicity, need to be developed.

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“…A proliferation of the sarcoplasmic reticulum with vacuolizations similar to that occurring with anthracyclines was also reproted with 5-Fu. [38,43] According to Labianca et al, [44] the global incidence of heart lesions associated with 5-Fu is higher in patients with a cardiac history in comparison to patients with no cardiac history (4.5 versus 1.1%). [44] The risk of 5-Fu cardiotoxicity was increased in 5-Futreated patients receiving mediastinal radiotherapy.…”

Section: Mechanism Of 5-fluorouracil Cardiotoxicitymentioning

confidence: 99%

“…[38,43] According to Labianca et al, [44] the global incidence of heart lesions associated with 5-Fu is higher in patients with a cardiac history in comparison to patients with no cardiac history (4.5 versus 1.1%). [44] The risk of 5-Fu cardiotoxicity was increased in 5-Futreated patients receiving mediastinal radiotherapy. [45] However Tsibiribi et al [43] described cardiac complications in 16 out of 1350 patients treated with 5-Fu with a negative history of diseases of the cardiovascular system.…”

Section: Mechanism Of 5-fluorouracil Cardiotoxicitymentioning

confidence: 99%