levoleucovorin and Coronary-Vasospasm

Colorectal cancer (CRC) represents a major public health problem accounting for > 1 million cases of new cancers and about half a million deaths worldwide. The risk of recurrence remains high despite curative surgery in early disease stages. The incremental benefit in absolute recurrence-free survival from 5-fluorouracil (5-FU)-based regimens in young patients with high-risk colon cancer is not insignificant. We present a case of a 57-year-old otherwise healthy white man who was treated with adjuvant chemotherapy consisting of modified 5-FU/leucovorin/oxaliplatin (FOLFOX6) regimen for stage III colon cancer. He experienced significant cardiotoxicity related to infusional 5-FU. Because of his young age and high-risk cancer, the patient opted to continue with adjuvant bolus 5-FU-containing chemotherapy after a lengthy discussion. With close cardiac monitoring and treatment with calcium channel blocker to prevent coronary vasospasm, he was able to successfully complete adjuvant chemotherapy. Currently, there are no guidelines for predicting a patient's risk for 5-FU-induced cardiotoxicity. Similarly, there is no uniform management of this 5-FU-related induced cardiotoxicity. We believe that our case report, with a brief review of related literature, might help fill some of this vacuum.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Coronary Vasospasm; Electrocardiography; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Myocardial Stunning; Neoplasm Staging; Organoplatinum Compounds

Cardiotoxicity is a rare but serious complication of 5-fluorouracil therapy. Coronary vasospasm and, less frequently, acute myocarditis have been identified as underlying mechanisms. We report a case of severe toxicity in a relatively young and fit male patient being treated for metastatic colonic adenocarcinoma displaying characteristics that cannot be explained by either mechanism alone.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Cardiovascular Agents; Colonic Neoplasms; Coronary Vasospasm; Fluorouracil; Heart Diseases; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Myocarditis; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome; Ventricular Dysfunction, Left

5-Fluorouracil (5-FU), a known cardiotoxin, is the backbone for the treatment of colorectal cancer. It is associated with arrhythmias, myocardial infarction and sudden cardiac death. Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium.A woman with metastatic colon cancer, originally treated with a 5-FU infusion as part of the FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) regimen, was unable to tolerate the chemotherapy due to chest pain. She was transitioned from infusional 5-FU to inferior 1-hour bolus 5-FU, in an attempt to minimise cardiotoxicity, but had disease progression. A multidisciplinary decision was made to again trial 5-FU infusion and pretreat with diltiazem. She tolerated chemotherapy without adverse events. A multidisciplinary discussion is recommended for co-management of reversible 5-FU-associated cardiotoxicity. After coronary artery disease (CAD) risk stratification and treatment, empiric treatment with calcium channel blockers and/or nitrates may allow patients with suspected coronary vasospasm, from 5-FU, to continue this vital chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Calcium Channel Blockers; Camptothecin; Cardiotoxicity; Cardiotoxins; Colorectal Neoplasms; Coronary Vasospasm; Diltiazem; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Nitrates

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Chemotherapy, Adjuvant; Colonic Neoplasms; Coronary Vasospasm; Diltiazem; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Nifedipine; Organoplatinum Compounds; Vasodilator Agents

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, condition. The case of an 83-year-old man with colon cancer who developed chest pain during 5-FU infusion is presented. The electrocardiogram (ECG) showed pronounced ST elevation in the lateral leads, and the chest pain was resolved after infusion of nitroglycerin. A coronary angiogram (CAG) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery. Coronary artery spasm with fixed stenosis was considered, and a drug-eluting stent was implanted. After 8 hours, the patient complained of recurring chest pain, paralleled by ST elevation on the ECG. The chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine. Repeated CAG showed patency of the previous stent. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-FU cardiotoxicity.

Topics: Aged, 80 and over; Angina Pectoris; Antineoplastic Combined Chemotherapy Protocols; Calcium Channel Blockers; Colonic Neoplasms; Coronary Angiography; Coronary Vasospasm; Drug-Eluting Stents; Electrocardiography; Fluorouracil; Humans; Leucovorin; Male; Nifedipine; Nitroglycerin; Organoplatinum Compounds; Percutaneous Coronary Intervention; Recurrence; Severity of Illness Index; Treatment Outcome; Vasodilator Agents

Topics: Adenocarcinoma; Administration, Oral; Adult; Antimetabolites, Antineoplastic; Cecal Neoplasms; Coronary Angiography; Coronary Disease; Coronary Vasospasm; Diltiazem; Duodenal Neoplasms; Echocardiography; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Nitrates; Vasodilator Agents

The frequently used chemotherapeutic drug 5-fluorouracil (5-FU) is known to cause angina pectoris and arrhythmias; myocardial infarction and sudden cardiac death could occur. Potential reasons for these phenomena range from toxic/metabolic disturbances to coronary artery spasms. This report shows angiographically proven spasmophilia of the coronary arteries and contributes to the understanding of angina pectoris occurring during treatment with 5-FU. Thus, verapamil type calcium antagonists as well as nitrates should be administered primarily in patients with coronary artery disease and in all patients who had been symptomatic during 5-FU administration in order to prevent further episodes.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Coronary Angiography; Coronary Circulation; Coronary Vasospasm; Electrocardiography; Esophageal Neoplasms; Esophagectomy; Exercise Test; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Regional Blood Flow

Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5-FU treatment.. Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled. P maximum (P max), P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration) were measured from the 12-lead ECG at the 0th and 48th hour of the first chemotherapy cycle. Echocardiography was also obtained in all patients at the same times.. Clinical cardiotoxicity was observed in two patients. P max and Pd were both significantly longer after 5-FU treatment at the 48th hour (P < 0.001). P min did not change (P > 0.05).. Treatment with 5-FU based regimens may increase Pd and prolong the P max in cancer patients. These alterations may be predictive of patients at risk of atrial arrhythmias during 5-FU treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Carcinoma; Colorectal Neoplasms; Coronary Artery Disease; Coronary Vasospasm; Coronary Vessels; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography; Electrocardiography; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Stomach Neoplasms; Time Factors