9/17/2023 0 Comments Keymo alternative![]() ![]() In one study, seven out of 300 patients manifested cardiac toxicity after administration of 5-FU with prophylactic nitroglycerin which failed to prevent EKG changes suggestive of myocardial ischemia during repeat infusion. Two older studies looked at nitroglycerine and nifedipine and diltiazem. 2 Investigators have also evaluated the use of anti-anginal drugs with 5-FU and capecitabine. 2,– 7 – 9 Additionally, approximately 13% of patients died upon being re-exposed to 5-FU. Previous studies have alarmed that rechallenging a patient with previous 5-FU cardiotoxicity with either a lower dose or another mode of administration could result in repeat of cardiac complication in up to 45% of patients. 2, 4 Reports include both chemo-naïve patients as well as those rechallenged after developing cardiac toxicity to 5-FU. 2 – 8 We presented a met-analysis in 2001 which revealed that cardiac toxicity was associated with the longer duration of 5-FU administration and later we found similar toxicities associated with capecitabine, that mimics medium duration of the infusion. 2 – 4, 7 However, the majority of the cases reported previously had no such risk factors identified except few proposing an increased risk with concomitant administration of certain chemotherapeutics, such as 5-FU when used with cisplatin, or prior chest radiation, or combination of capecitabine with oxaliplatin and bevacizumab. Several studies have also attempted to identify factors that might alter the incidence or severity of 5-FU-induced cardiac toxicity, including age, prior history of coronary artery disease, presence of comorbidities (smoking, hypertension, diabetes), and concomitant administration of other chemotherapeutic agents or radiation therapy. This article is licensed under a Creative Commons Attribution 4.0 International License. Mechanisms of cardiac toxicities associated with 5-FU/capecitabine Adapted from Shiga, T, Hiraide, M Cardiotoxicities of 5-Fluorouracil and Other Fluoropyrimidines. These statistics further underline the importance of recognizing and managing the cardiac toxicity associated with 5-FU and its analogs.Ĭlinical manifestations of cardiac complications of fluoropyrimidines may include angina, myocardial infarction, arrhythmias, hypotension, Tako-Tsubo syndrome, heart failure, cardiogenic shock, pericarditis, and even sudden death, 2, 4 as summarized in Table 1. Additionally, 5-FU administration continues in the second-line after progression in combination with other agents, eg FOLFOX to FOLFIRI. Moreover, 5-FU is usually administered for a series of cycles up to 6 months in adjuvant setting and till progression in advanced stages. Intravenous 5-FU is administered to nearly 275,000 cancer patients per year and capecitabine is taken by an additional 30,000 patients per year in the US. ![]() 5-FU is usually given orally or intravenously as a bolus or by continuous intravenous infusion and as a topical application. Cardiotoxicity associated with either 5-FU or capecitabine is of utmost significance for many reasons. 1 As we continue to use these agents commonly, recognition of its related uncommon or under-recognized toxicities such as cardiac toxicity has also improved. Switching to a non-fluoropyrimidine-containing chemotherapy regimen is usually the most feasible choice for patients with metastatic disease as data on adjuvant setting is usually a fluoropyrimidine or its combination with oxaliplatin at present.įluoropyrimidines remain to be the backbone of regimens to treat many common solid tumors, including head and neck (H&N), breast, pancreas, stomach, anus, skin, small bowel, and especially colorectal cancer. The author describes here treatment options for patients with metastatic colorectal cancer who have encountered fluoropyrimidine-induced cardiotoxicity, including switching to a different fluoropyrimidine, switching to a different schedule of intravenous 5-FU, or switching to a non-fluoropyrimidine-containing chemotherapy regimen if one exists. ![]() Cardiotoxicity is unpredictable and no alternative chemotherapeutics have been defined so far. Clinical manifestations of cardiac complications of fluoropyrimidines including angina, myocardial infarction, arrhythmias, hypotension, Tako-Tsubo syndrome, heart failure, cardiogenic shock, pericarditis, and even sudden death have been reported. Nearly 13% of patients died upon re-exposure to 5-FU. Previous studies also concluded that rechallenging a patient with previous 5-FU cardiotoxicity with either lower dose or another mode of administration could result in repeat of cardiac complication in up to 45% of patients. The incidence of cardiotoxicity associated with 5-FU ranges from 1.5–18%. 5-Fluorouracil (5-FU) remains to be the backbone of chemotherapy regimens approved for treatment of colorectal cancer and other gastrointestinal cancers and breast cancer. ![]()
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