Vascular events in patients receiving high‐dose infusional 5‐fluorouracil‐based chemotherapy: The University of Chicago experience

Gradishar, WJ; Vokes, Everett E.; Schilsky, Richard L.; Weichselbaum, Ralph R.; Panje, William R.

doi:10.1002/mpo.2950190103

Cited by 22 publications

(7 citation statements)

References 36 publications

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“…An increased incidence of thrombotic vascular events, rang ing from cardiac arrhythmias to sudden death, have also been reported to occur concurrently with 5-FU infusion or after its completion [11], All of our patients who developed symptomatic car diotoxicity received concomitant chemotherapy. Five pa tients had concomitant cisplatin and 3 received mitomycin c. Therefore we cannot rule out the contribution of these agents to cardiotoxicity.…”

Section: Discussionsupporting

confidence: 52%

Symptomatic Cardiotoxicity with High-Dose 5-Fluorouracil Infusion: A Prospective Study

Akhtar

Salim²,

Bano³

1993

Oncology

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Cardiotoxicity with 5-fluorouracil (5-FU) therapy has been reported to range from asymptomatic EKG abnormalities to fatal myocardial infarction. We report a prospective study in 100 consecutive patients receiving 5-FU infusion in combination with other chemotherapeutic agents or alone for the treatment of different malignancies with the aim of identifying patients who develop symptomatic cardiotoxicity. Patients with a history of cardiac illness, abnormal EKG or cardiac enzyme levels were excluded. Patients were observed during the total period of infusion, daily EKG was performed on asymptomatic patients, those who developed cardiotoxicity were monitored till symptom-free for 24 h. Eight patients developed symptoms suggestive of cardiotoxicity. Pain was the commonest symptom (5/8), followed by palpitation and sweating. Three patients developed EKG abnormalities and 1 went into cardiogenic shock. Time to toxicity ranged from 18 to 30 h (mean 24 ± 3.7 h) and serial cardiac enzyme levels remained normal in all patients. The symptoms reversed immediately on cessation of the treatment in most of the patients (7/8). Time to recovery ranged from 5 to 60 min (mean 19.28 ± 19.6 min). There was no recorded death due to toxicity. We conclude that 5-Fu infusion is associated with a significant risk of symptomatic cardiotoxicity. Concomitant chemotherapeutic agents, received by all the affected patients, may have a contributory effect too. Cardiotoxicity seems to be completely reversible, particularly in patients without underlying cardiac disease. The patients should be informed about the symptoms and the condition recognised and managed immediately.

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Section: Discussionsupporting

confidence: 52%

Symptomatic Cardiotoxicity with High-Dose 5-Fluorouracil Infusion: A Prospective Study

Akhtar

Salim²,

Bano³

1993

Oncology

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“…The individual severity of events with 3 toxic deaths is far from negligible. In addition, if continuous monitoring had been ap plied, the frequency of silent ischemic reactions might have been substantially higher, as could be documented for the com bination 5-FU/cisplatin [7,8,11], Although the type of toxicity does not seem to be altered with the combination of 5-FU and folinic acid, there is a significant trend towards a later onset of symptoms. The average received dose is thus the same although the dose of 5-FU was reduced to conventionally dosed 5-FU bolus monotherapy.…”

Section: Discussionmentioning

confidence: 95%

“…Prospective studies involving cardiologic pre-study evaluations and close monitoring with continuous 24-hour ECG tracings are missing in patients undergoing 5-FU single-agent therapy. Significant clinical symptoms are almost uniformly reported as anginal pain resembling myocardial ischemia associated with or without specific ECG findings, to a lesser extent arrhyth mias, ventricular dysfunction, transmural infarction and even occasional deaths [6][7][8][9][10]. But silent ischemic episodes could be documented in approximately 15% of patients followed pros pectively with 24-hour ECG monitoring undergoing therapy with 5-FU/cisplatin [11], Thus, concerning both incidence and severity, the cardiovas cular side effects of 5-FU-containing regimens are far from negligible, even more so if the wide application of 5-FU as ad juvant and therapeutic drug for a variety of cancers in cohorts of patients is taken into consideration.…”

Section: Introductionmentioning

confidence: 99%

“…Because cardiac side effects are being reported with a variety of antitumor agents, the contributing role of each drug in com bination with 5-FU is hardly assessable. The combination of continuous infusion of 5-FU plus cisplatin in head and neck and esophageal cancer especially seemed to be hampered with an excessive risk of severe cardiac complications which might be either inherent to this particular schedule or the patient pop ulation which has in itself a high incidence of cardiovascular risk factors [6][7][8][9]. In fact, a preceding cardiac history is con sidered to be the most important risk factor in 5-FU-induced cardiotoxicity [5].…”

Section: Introductionmentioning

confidence: 99%

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Cardiotoxicity Associated with 5-Fluorouracil Single-Agent Therapy

Schöber¹,

Schmoll²

1993

Oncol Res Treat

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The aim of this report is to define the characteristics of the cardiovascular syndrome associated with the use of 5-fluorouracil (5-FU) single-agent therapy based on a review of the literature. 38 patients were identified and evaluated according to their pretreatment characteristics, symptomatology, clinical findings and management following treatment. Clinical symptoms appeared within a few days following the termination of the first treatment cycles and consisted in more than 90% of affected patients in severe, reproducible anginal pain (WHO grade 3) resembling myocardial ischemia with coinciding temporarily ischemic changes on ECG. However, transmural infarction was only diagnosed in 4 patients (11%). 3 patients (9% of those affected) died in close association to 5-FU administration. Arrhythmias and hypotension were less frequent. The symptoms were self-limiting in most patients. Efficacy of treatment or prophylaxis with nitrates or calcium channel blockers was unpredictable. The addition of folinic acid to 5-FU in an own cohort of 339 patients with gastrointestinal cancers does not add to the cardiotoxic potential nor does it change the spectrum of signs and symptoms.

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“…30,31,32,33 Calcium channel blockers appear to be effective in treating patients who exhibit vasospasm or worsening angina while receiving 5-FU. 34 Cisplatin An association has been reported between cisplatin treatment and increased cardiovascular death rates, including sudden death in young men treated with combination chemotherapy for germ cell tumors. 35,36 Taxanes Paclitaxel (Taxol) and docetaxel (Taxotere), act to stabilize microtubules.…”

Section: -Fluorouracil (5-fu)mentioning

confidence: 99%