Medline ® Abstracts for References 18,38
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study.
Kosmas C, Kallistratos MS, Kopterides P, Syrios J, Skopelitis H, Mylonakis N, Karabelis A, Tsavaris N
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.
Department of Medicine, 2nd Division of Medical Oncology, "Metaxa" Cancer Hospital, Piraues, 21 Apolloniou Street, 16341 Athens, Greece. firstname.lastname@example.org
A retrospective study of cardiotoxicities induced by 5-fluouracil (5-FU) and 5-FU based chemotherapy regimens in Pakistani adult cancer patients at Shaukat Khanum Memorial Cancer Hospital&Research Center.
Khan MA, Masood N, Husain N, Ahmad B, Aziz T, Naeem A
J Pak Med Assoc. 2012 May;62(5):430-4.
OBJECTIVE: To study cardiotoxicities, especially bradycardia in cancer patients treated with 5-Fluouracil and 5-Fluouracil based chemotherapy regimens in Pakistani population.
METHODS: Data was extracted from the medical records of all diagnosed cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Center registered between January 2002 and December 2004 receiving 5- Fluouracil based chemotherapy regimens. The data was analysed retrospectively, including electrocardiogram and cardiac markers. Pearson's Correlation coefficient was calculated to see any possible correlation between 5-Fluouracil alone and 5-Fluouracil based regimens and cardiotoxicity, and other variables.
RESULTS: Symptomatic cardiotoxicity was observed in 60 (19.93%) out of 301 patients whose cases were part of the study. Bradycardia was the most common cardiotoxicity and was observed in 36 (11.96%) patients. Nine (2.99%) mortalities were also observed. The incidence of cardiotoxicity was not significantly different between the patients with and without pre-existing cardiovascular disease (p = 0.095) and having negative correlation - 0.305. Cardiotoxicities were more common with Continuous Infusion (CI) of 5-Fluouracil, radiotherapy concurrent with 5-Fluouracil and when 5-Fluouracil was used in combination with Cisplatinum (CDDP).
CONCLUSION: Cardiotoxicities were more prevalent when 5-Fluouracil was used along with concurrent radiotherapy and with Cisplatinum and when administered in continuous infusion pattern. Hence, 5-Fluouracil and 5-Fluouracil based chemotherapy regimens cause cardiotoxicities, especially bradycardia, in a significant number of cancer patients in Pakistani population.
Department of Adult Oncology/Hematology, National Guard King Khalid Hospital, KAMC-WR, Jeddah, KSA. email@example.com