Obesity, smoking tied to 5-FU-induced cardiotoxicity in cancer patients

Smoking, obesity, treatment duration, and pre-existing cardiac diseases may contribute to the development of cardiotoxicity among patients with cancer who are undergoing 5-fluorouracil (5-FU) chemotherapy, suggests a recent study.

“[W]ell-defined risk factors and their possible mechanisms should be identified and evaluated on a clinical basis and put together into a model for risk stratification, which could be used by clinicians to aid their decisions during treatment schedules for patients undergoing 5-FU based chemotherapy,” the investigators said. 

A total of 396 patients were included in this prospective study conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. They were grouped according to the therapeutic protocol they received: 5-FU monotherapy or in combination, with different dosing regimens.

The investigators assessed 5-FU–induced cardiotoxicity using electrocardiography and serum troponin levels. When cardiotoxicity was detected, 5-FU treatment was ceased, and nitroglycerin, nitrates, and calcium channel blockers were given to the affected patients. Cardiac monitoring was also initiated. Treatment with 5-FU was stopped in those with acute myocardial infarction (MI).

More than one in four patients (28.5 percent) reported different cardiotoxic symptoms following treatment with various 5-FU–containing protocols. Of the patients, 35 percent had anginal pain, 13 percent suffered an MI, 11 percent developed hypertension, and 10 percent had heart failure. [J Oncol Pharm Pract 2025;doi:10.1177/10781552241275948]

Dose dependence

Cardiotoxic events among patients treated with 5-FU combination therapy were significantly different from those on 5-FU monotherapy. ECG results showed that only the QTc-d interval increased significantly (p<0.001) after therapy. Furthermore, many of the patients (68 percent) had troponin levels >2 ng/mL at the end of treatment.

“Our results showed that patients who were administered a 5-FU dose of 600–800 mg/m2 in different treatment regimens had a higher risk of developing cardiotoxicity than those who received low 5-FU doses of 200–400 mg/m2 (initial dose),” the investigators said. “This suggests that the cardiotoxic events associated with 5-FU administration could be dose-dependent.” 

The dose dependence of 5-FU–related cardiotoxicity remains unclear, as suggested by existing literature, but the current findings are similar to those reported in another study, in which patients receiving 5-FU dose >600 mg/m2 had a high likelihood of developing cardiac toxicity. [J Urol 1991;146:1418-1424; J Clin Pharm Ther 2004;29:267-271; Curr Treat Options Oncol 2020;21:1-21]

“Patient monitoring and management of cardiotoxic events during 5-FU administration are crucial steps [during] treatment to avoid further complications and lower mortality rates,” the investigators said.

The current study also showed that obesity and smoking may increase the incidence and complications of 5-FU–related cardiotoxicities.

"Hence, patients who receive 5-FU should be advised to stop smoking and maintain a healthy weight, as they are at a higher risk of developing cardiotoxicity after taking 5-FU drug if they are overweight or obese and smokers,” the investigators said. 

"[A] wide range of clinical trials should be conducted to assess and evaluate the various risk factors indicated in the present study, as well as previous studies, and their clinical utility should be demonstrated,” they added.