UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstracts for References 8,55,104,107

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

8
TI
Fluoropyrimidine-associated cardiotoxicity: revisited.
AU
Saif MW, Shah MM, Shah AR
SO
Expert Opin Drug Saf. 2009;8(2):191.
 
BACKGROUND: The syndrome of 5-fluorouracil (5-FU)-associated cardiotoxicity remains poorly defined.
PATIENTS AND METHODS: We performed a literature review (1969 - 2007) and compiled data derived from 377 evaluable cases out of 448 reported cases.
RESULTS: Patient age ranged from 14 to 86 years. Of the patients 65% were 55 years old and the male:female ratio was 1.5:1. The most commonly treated tumors were gastrointestinal (60%), head and neck (22%) and breast (4%). Of the patients 14% had a history of heart disease whereas cardiac risk factors were found in 37%. Mode of administration included: continuous infusion (72%); bolus (22.5%); intermediate infusion (3%); oral (2%); and intraperitoneal (1 patient). The dosages of 5-FU used were<750 mg/m(2)/day (36%), 751 - 999 (16%), 1,000 (26%), 1,001 - 1,499 (4%) and 1,500 (16%). Of the patients 54% received 5-FU in combination with other chemotherapeutic agents (cisplatin 44%) whereas 51% received 5-FU alone or with leucovorin. Only 4% patients had undergone previous or concomitant radiation therapy to the mediastinum. Of cardiac incidents that happened 69% were seen during or within 72 h of the first cycle of 5-FU. Angina occurred in 45% ofpatients whereas myocardial infarction was seen in 22%, arrhythmias in 23, acute pulmonary edema in 5, cardiac arrest and pericarditis in 1.4 and heart failure in 2. Electro-cardiographic evidence of ischemia or ST-T changes were recorded in 69% of patients, but abnormal cardiac enzymes were found in only 12%. The cardiac symptoms were reproducible in 47%, including in one patient subsequently treated with 5-FU p.o. Symptoms were also elicited when the same patients were treated with lower doses or different schedules. Of the patients 68% responded to conservative anti-anginal therapy, although prophylactic coronary vasodilators had limited efficacy. Overall, 8% of patients showing cardiotoxicity on 5-FU administration died. Furthermore, 13% reexposed to 5-FU died.
CONCLUSIONS: Our review suggests that 5-FU cardiotoxicity is an infrequent but real phenomenon that is independent of dose and may be related to a continuous infusion schedule. The presence of cardiac risk factors is not predictive. Patients should be observed closely and 5-FU administration discontinued if cardiac symptoms develop. A rechallenge with 5-FU should be reserved only for those patients in whom there is no reasonable alternative therapy and should be performed in the setting of aggressive prophylaxis and close monitoring.
AD
Yale University School of Medicine, FMP 116, CT 06520, New Haven, USA. wasif.saif@yale.edu
PMID
55
TI
Rechallenging 5-Fluorouracil in a Patient With Capecitabine-Induced Ventricular Fibrillation.
AU
Lai S, Marshall JL, Morrissey RL
SO
Clin Colorectal Cancer. 2015 Sep;14(3):198-201. Epub 2015 Mar 6.
 
AD
Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC. Electronic address: laisueyi@gmail.com.
PMID
104
TI
Bolus 5-Fluorouracil as an alternative modality to infusion 5-Fluorouracil in a patient with rectal cancer and capecitabine-induced cardiotoxicity.
AU
Shaib W, Lee V, Saif MW
SO
In Vivo. 2009;23(5):821.
 
5-Fluorouracil (5-FU) is the backbone of the chemotherapy regimens approved for treatment of colorectal cancer. Incidence of cardiotoxicity associated with 5-FU ranges between 1.5% to 18%; 48% as anginal symptoms and 2% as cardiogenic shock. Cardiotoxicity is unpredictable and no alternatives have been defined so far. A 35-year-old man treated for stage III A rectal cancer developed chest pain typical of angina on treatment with capecetabine initially and 5-FU infusion afterwards. Scheduled dosing of 5-FU was changed from infusion to a bolus type. He was asymptomatic with no electrocardiographic (ECG) changes on 24-h Holter monitoring after changing the mode of administration to bolus 5-FU. Here, we report the first case in the English literature where a change in the mode of 5-FU administration to bolus is an alternative to infusion 5-FU-induced cardiotoxicity. In conclusion, Bolus 5-FU can be used in patients developing cardio-toxicity due to 5-FU infusion.
AD
Hospital of Saint Raphael, New Haven, CT, USA.
PMID
107
TI
A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxic effects: potential for an individualized medicine approach.
AU
Saif MW, Lee AM, Offer SM, McConnell K, Relias V, Diasio RB
SO
Mayo Clin Proc. 2014;89(1):131.
 
5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect-associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry.
AD
Division of Hematology/Oncology and Experimental Therapeutics, Tufts Medical Center, Boston, MA. Electronic address: wsaif@tuftsmedicalcenter.org.
PMID