levoleucovorin and Cardiotoxicity

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

Methotrexate is an antifolate antimetabolite that inhibits the activity of dihydrofolate reductase by acting as a false substrate, which leads to defects of DNA synthesis, specifically the inhibition of purine and pyrimidine synthesis. Thus, methotrexate is a powerful agent for treating autoimmune diseases and cancer. In general, methotrexate is thought to be cardioprotective and reports of methotrexate-induced cardiomyopathy are rare. We present a case of methotrexate-induced severe cardiotoxicity diagnosed by exclusion of all other potential causes.. The patient was a 54-year-old Caucasian man presenting to an outside hospital with a chief complaint of abdominal pain and bloating who reported taking methotrexate up to 20 mg per week for systemic sclerosis. After a transthoracic echocardiogram found a left ventricular ejection fraction of 10% and coronary catheterization demonstrated no significant disease, he was transferred to our hospital for advanced heart failure therapies. His condition deteriorated, and he was eventually placed on veno-arterial extracorporeal membrane oxygenation. Owing to a lack of an identifiable etiology of cardiac failure, toxicology consultation recommended 24 hours of intravenous leucovorin therapy to overcome any residual and potentially cardiotoxic methotrexate still in his system. Over the next 5 days, his cardiac function improved daily, such that on day 5 of extracorporeal membrane oxygenation, he had a left ventricular ejection fraction of 40% and was able to be decannulated. Two days later, his ejection fraction improved to 60% and normal right ventricular function. Initially, his renal function improved while on extracorporeal membrane oxygenation, but over the next week deteriorated such that he required intermittent hemodialysis until hospital discharge.. After a process of elimination, the most likely cause of this patient's acute decline and rapid recovery of bi-ventricular function was methotrexate toxicity. Leucovorin may have aided the reversal of methotrexate toxicity.

Topics: Cardiotoxicity; Extracorporeal Membrane Oxygenation; Heart Failure; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Stroke Volume; Ventricular Function, Left

To evaluate the changes in left ventricular myocardial function in patients with colorectal cancer undergoing chemotherapy with mFOLFOX6 (oxaliplatin + 5-fluorouracil + calcium folinate) using three-dimensional speckle-tracking echocardiography (3D-STE). Data were collected from 30 patients diagnosed with colorectal cancer in our hospital treated with mFOLFOX6. We used 3D-STE to measure the following parameters of left ventricle function: global longitudinal strain (GLS), global area strain (GAS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw). Myocardial composite index (MCI) was calculated from measured values (MCI = GLS × LVtw). The above listed parameters were compared before and after chemotherapy. Receiver operating curves (ROC) were prepared for each parameter and analyzed to identify correlations among MCI, LVEF, GLS, and cTnT. Compared with the pre-chemotherapy state, the absolute values of MCI, LVtw, GLS, GAS, GCS, and GRS decreased with increasing cumulative doses of chemotherapeutic drugs. The absolute values of GAS, GLS, MCI, and LVtw decreased after the first cycle of chemotherapy (P < 0.05). The areas under the ROC curves for MCI and GLS were 0.903 and 0.838, respectively. The correlation observed between MCI and cTnT (r = - 0.7228) was found to be stronger than that between GLS and cTnT (r = - 0.6008). In conclusion, 3D-STE may help detect early changes in left ventricular myocardial function caused by mFOLFOX6 treatment in patients with colorectal cancer. MCI is a relatively sensitive index among the various measurable parameters.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomechanical Phenomena; Cardiotoxicity; Colorectal Neoplasms; Early Diagnosis; Echocardiography, Doppler; Echocardiography, Four-Dimensional; Female; Fluorouracil; Heart Diseases; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Predictive Value of Tests; Time Factors; Ventricular Function, Left

BACKGROUND 5-Fluorouracil (5-FU) is a widely used intravenous chemotherapy agent that is highly effective in the treatment of a variety of solid malignancies. Cardiotoxicity related to 5-FU is a complex clinical entity associated with significant morbidity and mortality. Whether a patient who experienced a major cardiac side effect from 5-FU can be safely rechallenged with this drug is a clinical dilemma. CASE REPORT We present the case of a patient with stage III colorectal adenocarcinoma who experienced ventricular fibrillation during the first cycle of FOLFOX (5-FU, folinic acid, and oxaliplatin) regimen in the adjuvant setting. Post-resuscitation electrocardiogram revealed ST-elevation in the inferior leads with reciprocal changes. Coronary angiogram revealed no obstructive coronary artery disease. Cardiac workup led to the conclusion of probable fluorouracil-induced vasospasm as the cause of his cardiac arrest. He received implantable cardioverter defibrillator. The decision was made to hold 5-FU. At 3-month follow-up, there was evidence of progressive metastasis. After comprehensive risk-benefit discussions, the decision was made for palliative chemotherapy using 5-FU/leucovorin. A pre-treatment regimen including isosorbide dinitrate, diltiazem, and metoprolol was used. The patient tolerated 5-FU rechallenge without recurrent cardiovascular complication. CONCLUSIONS The cardiotoxicity profile of 5-FU can range from anginal chest pain to sudden cardiac death. When considering 5-FU rechallenge, clinicians should adopt a multidisciplinary approach, favor using prophylactic antianginal therapy, change to bolus dosing, and use continuous telemetry monitoring. Screening patients for dihydropyrimidine dehydrogenase deficiency prior to 5-FU administration may facilitate an individualized strategy for optimal dosing and safety.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Male

5-Fluorouracil (5-FU) represents the backbone of systemic therapy regimens of colorectal cancer. The current study aims at evaluating the patterns and predictors of cardiac adverse events associated with various 5-FU-based systemic therapy regimens among patients with metastatic colorectal cancer.. This pooled analysis includes de-identified patient-level datasets from 5 randomized studies (NCT00272051, NCT00305188, NCT00115765, NCT00364013, and NCT00384176). In order to evaluate factors predicting the development of all cardiac toxicities, arrhythmias, and ischemic events, univariate logistic regression analysis was conducted. Subsequently, factors with P < .05 in univariate analysis were included in multivariate logistic regression analysis.. A total of 3223 patients were included in the pooled analysis. A total of 255 (7.9%) patients developed some form of a cardiac toxicity, among which 153 (4.7%) patients developed some form of arrhythmia and 62 (1.9%) patients developed an ischemic event. Within multivariate logistic regression analysis for factors predicting cardiac toxicities, only bevacizumab-containing regimens (P = .002) and panitumumab-containing regimens (P < .001) were predictive for the occurrence of cardiac toxicity. Similarly, within multivariate logistic regression analysis for factors predicting cardiac arrhythmias, only panitumumab-based regimens were predictive of the occurrence of arrhythmias (P < .001). Likewise, within multivariate logistic regression analysis for factors predicting cardiac ischemia, only bevacizumab-containing regimens were predictive of ischemic events (P = .004).. Bevacizumab- and panitumumab-containing regimens seem to be associated with a higher risk of cardiac toxicities compared with other 5-FU-based regimens. Bevacizumab-containing regimens seem to increase the risk of 5-FU-related ischemic events, whereas panitumumab-containing regimens seem to increase the risk of arrhythmias.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cardiotoxicity; Cardiovascular Diseases; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Oxaliplatin; Panitumumab; Prognosis; Randomized Controlled Trials as Topic

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