Short summary

As more survive cancer treatment the matter of toxic side effects has become increasingly relevant. Focus has been on anthracycline and Herceptin but 5-FU is considered to be one of the most cardiotoxic chemotherapeutic agents as well. The use of 5-FU is increasing why it is clinically relevant to understand the mechanisms of cardiotoxicity, to screen patients to predict side effects, and to take proper care of the patients with cardiac symptoms from their 5-FU treatment. The project is part of focused effort to improve cancer survivorship by reducing early and late toxicity. Above all, the objective is to prevent the cardiac symptoms by testing a new preventive strategy. 

Rationale

Cancer and cardiovascular diseases are the two most common causes of mortality and morbidity but still the therapeutic successes increase and so does long-term survival. Hence, the coexistence of cancer and cardiovascular disease in the individual patient is increasing in incidence and leading to debilitation.

5-fluorouracil (5-FU) is frequently used in the treatment of different solid cancers including gastrointestinal tumors. In Denmark it is recommended as standard care of metastatic colorectal cancer, often in combination with other therapies.

Unfortunately, 5-FU has cardiotoxic side effects. It is known to cause anginal chest pain or rarely even acute myocardial infarction, palpitations (due to several possible arrhythmias), dyspnoea, hypotension and heart failure. Symptoms occur in up to 35% of patients receiving 5-FU but subclinical manifestations have also been recognized in 4-88%. Angina pectoris is the most reported side effect to 5-FU.

Risk factors for ischemic heart diseases may predispose to these cardiotoxic events. However, the literature shows divergent results on predisposing factors.

Often evaluations contain blood samples, ECG or simple echocardiography but more advanced equipment is widely available. Coronary artery calcium score (CAC) obtained by cardiac CT scanning is a possible strategy to predict cardiotoxicity.  CAC reflects the total burden of atherosclerotic coronary plaques that may cause either stenosis resulting in angina pectoris or plaque rupture causing acute coronary syndromes. CAC above the age and gender adjusted median is used as cut off point for preventive medical intervention in ongoing cardiovascular screening trials, and a CAC of  more than 400 significantly increases the risk of cardiovascular events.

The aim is to evaluate CAC as a predictor of cardiac toxicity.

Description of the cohort

Cancer patients without cardiac symptoms undergoing chemotherapy with 5FU. 

Data and biological material

Clinical and demographic data.

Collaborating researchers and departments

Department of Cardiology, Vejle Hospital, Denmark

• Mads Dam Lyhne, MD
• Consultant Vibeke Brogaard Hansen, MD, PhD
• Consultant Lone Due Vestergaard, MD
• Consultant Lars Henrik Jensen, MD, PhD
• Martin Busk, MD, PhD, consultant
• Consultant Flemming Hald Steffensen, MD, PhD

Department of Oncology, Vejle Hospital, Denmark

• Associate Professor Lars Henrik Jensen