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Medline ® Abstracts for References 18,30-33

of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'

18
TI
Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study.
AU
Kosmas C, Kallistratos MS, Kopterides P, Syrios J, Skopelitis H, Mylonakis N, Karabelis A, Tsavaris N
SO
J Cancer Res Clin Oncol. 2008 Jan;134(1):75-82. Epub 2007 Jul 17.
 
BACKGROUND: Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration.
PATIENTS AND METHODS: Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with>two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment.
RESULTS: Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3-10.1%]than the remaining (7/317; 2.3%, 95% CI = 0.8-3.3%) (P<0.012). Specifically, an increased incidence of cardiac-related events was encountered in patients with continuous 24-h 5FU + LV infusion for 5 days (12.5%, 95% CI = 2.3-22.7%) rather than in patients with the same schedule without LV (5.3%, 95% CI = 1.95-8.67%) (P<0.027), as well as in patients with short 5FU + LV administration (2.4%, 95% CI = 0.9-3.9%) (P<0.019). Overall, 3/54 patients (5.5%, 95% CI = -0.6-11.1%) on oral capecitabine developed cardiac-related events. Seven out of the 20 patients suffered an acute myocardial infarction, 6 developed ischemia only, while 4 more patients had ECG consistent with coronary vasospasm and 3 with conduction disturbances, of which one subsequently died. Patients administered oral capecitabine had a similar incidence of cardiac-related events; 1/22 (4.5%) patients with advanced breast cancer and 2/32 (6.2%) with colorectal cancer.
CONCLUSIONS: The present study supports the toxic effect of 5-FU on the myocardium, which is largely schedule-dependent, whereas a low but finite risk of such toxicity has been observed with oral capecitabine. A high level of alertness is required when using fluoropyrimidines (i.v. 5FU or oral capecitabine), while their toxic effect on the coronary endothelium and myocardium merits further investigation.
AD
Department of Medicine, 2nd Division of Medical Oncology, "Metaxa" Cancer Hospital, Piraues, 21 Apolloniou Street, 16341 Athens, Greece. ckosm1@ath.forthnet.gr
PMID
30
TI
The frequency and pattern of cardiotoxicity observed with capecitabine used in conjunction with oxaliplatin in patients treated for advanced colorectal cancer (CRC).
AU
Ng M, Cunningham D, Norman AR
SO
Eur J Cancer. 2005;41(11):1542.
 
We examined the cardiotoxicity in 153 patients treated with capecitabine and oxaliplatin in two prospective trials for advanced colorectal cancer. Ten patients (6.5%) developed cardiac events. One patient (0.7%) had sudden death, one patient developed cardiac failure with raised troponin I while another developed ventricular tachycardia (VT). The remaining seven patients (4.6%) experienced angina and three of the seven patients had raised troponin I, one of which developed ventricular fibrillation. Eight events occurred within cycle 1 (median cycle 1 day 10). Four patients with angina and one patient with VT recovered on stopping capecitabine, four patients required additional medical management and the remaining patient died suddenly at home. Patients with ischaemic heart disease appeared to be at increased risk. Physicians and patients need to be aware of these complications, so that prompt discontinuation of treatment and appropriate interventions may be instituted.
AD
Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK.
PMID
31
TI
Incidence of cardiotoxicity with the oral fluoropyrimidine capecitabine is typical of that reported with 5-fluorouracil.
AU
Van Cutsem E, Hoff PM, Blum JL, Abt M, Osterwalder B
SO
Ann Oncol. 2002;13(3):484.
 
AD
PMID
32
TI
Capecitabine-related cardiotoxicity: recognition and management.
AU
Saif MW, Tomita M, Ledbetter L, Diasio RB
SO
J Support Oncol. 2008;6(1):41.
 
AD
Yale University School of Medicine, Section of Medical Oncology, New Haven, CT 06520, USA. wasif.saif@yale.edu
PMID
33
TI
Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group.
AU
Kwakman JJ, Simkens LH, Mol L, Kok WE, Koopman M, Punt CJ
SO
Eur J Cancer. 2017;76:93. Epub 2017 Mar 10.
 
BACKGROUND: The frequency of capecitabine-related cardiotoxicity has been reported to be low but includes serious adverse events. We conducted a retrospective analysis of the incidence and severity of capecitabine-related cardiotoxicity in different regimens in the treatment of metastatic colorectal cancer in three randomised phase 3 studies.
METHODS: We used data of cardiac events reported in the CAIRO, CAIRO2 and CAIRO3 studies of the Dutch Colorectal Cancer Group (DCCG) and analysed the incidence and severity of cardiac events in the different treatment regimens of the trials which all included the use of capecitabine. The following events were included: chest pain, newly diagnosed cardiac ischaemia/infarction, atrial fibrillation, other arrhythmias and heart failure, all graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC).
RESULTS: A total of 1973 patients were included, who received a total of2461 capecitabine-based lines of treatment. Overall, 5.9% of patients (n = 117) experienced at least one cardiac event, and 2.3% (n = 46) experienced at least one grade≥3 event. Three patients had two cardiac events. The most frequently observed cardiac event was ischaemia/infarction (2.9%, n = 57), followed by arrhythmias (2.0%, n = 40, including atrial fibrillation in 10 patients), chest pain (0.8%, n = 16) and heart failure (0.4%, n = 7). The highest incidence of cardiac events was observed in patients treated with capecitabine in combination with oxaliplatin and bevacizumab (12%, n = 43).
CONCLUSION: We observed capecitabine-related cardiotoxicity in 5.9% of patients, and severe cardiotoxicity in 2.3% of patients. Combination treatment with capecitabine, oxaliplatin and bevacizumab was associated with the highest risk of cardiotoxicity.
AD
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Mijbergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.j.kwakman@amc.uva.nl.
PMID