# Unveiling the Mechanisms for the Development of Cardiotoxicity Following Chemotherapy Regimens Administration for Primary Colorectal Cancer: A Systematic Review

## TL;DR

This review examines how chemotherapy for colorectal cancer can lead to heart problems and highlights the importance of monitoring patients' heart health during treatment.

## Contribution

The study systematically maps the mechanisms and prevalence of chemotherapy-induced cardiotoxicity in colorectal cancer treatment.

## Key findings

- Chemotherapy regimens like FOLFOX and 5-FU are linked to heart strain, arrhythmias, and heart failure.
- Echocardiography and biomarkers can detect cardiac toxicity early, allowing some patients to safely continue treatment.
- There is no standardized cardiac screening protocol for chemotherapy patients, emphasizing the need for routine monitoring.

## Abstract

The present systematic review explored how chemotherapy used to treat primary colorectal cancer, especially regimens like FOLFOX, CAPOX, and 5-FU/LV, can cause heart-related side effects. It includes 14 studies from various nations and unveiled that some individuals encountered minor concerns such as changes in heart strain, while others experienced more serious problems such as chest pain, arrhythmias, heart failure, or Takotsubo cardiomyopathy. Echocardiography and biomarkers were useful in detecting these alterations early. Case studies revealed that with careful monitoring and treatment, some patients were able to safely continue chemotherapy after recovering from cardiac toxicity. Overall, the study emphasizes the importance of regular cardiovascular exams before and during cancer therapy to improve patient safety and outcomes.

Background/Introduction: Colorectal carcinoma (CRC) belongs to the most commonly diagnosed malignancies to this date, ranking as third across the globe. In addition, CRC remains a leading cause of cancer-related deaths as it is ranked as the second most common cause of mortality. Therapeutic strategies for the management and treatment of CRC have made significant progress in the last two decades, with both adjuvant and neoadjuvant approaches playing critical roles in enhancing favorable outcomes with regimens like FOLFOX, CAPOX, and 5-FU-based therapies demonstrating effectiveness. Nevertheless, growing evidence indicates that these therapies may pose a risk of cardiotoxicity development. A systematic review will be conducted to map the mechanistic pathways of chemotherapy-induced in CRC in order to bridge oncology and cardiology perspectives, highlighting emerging diagnostic tools and long-term surveillance gaps. Purpose: The objective of this study is the investigation of the prevalence and characteristics of cardiovascular problems linked to frequently employed chemotherapy regimens, as well as to evaluate existing diagnostic and therapeutic approaches. Methodology: A thorough search across databases, including PubMed (MEDLINE), Embase, and Cochrane Library, was performed to locate articles published up to 2025. The final studies included in the review underwent quality assessment. Results: Fourteen qualifying studies, comprising both prospective trials and case reports from diverse geographies, were included. Cardiovascular outcomes including myocardial strain, arrhythmias, angina, heart failure, and Takotsubo cardiomyopathy were evaluated. The diagnostic methods assessed comprised echocardiography, cardiac biomarkers, and electrocardiograms. In the reviewed trials, chemotherapy-induced cardiotoxicity varied from asymptomatic ventricular strain to serious cardiac complications. The FOLFOX and 5-FU regimens were predominantly linked to adverse cardiac outcomes. Prompt identification by echocardiographic strain imaging and biomarker monitoring facilitated timely intervention. Case studies revealed that, given proper cardiological support, certain patients could safely recommence chemotherapy following recovery. No standardized cardiac screening protocol was identified among the trials. Conclusions: Chemotherapy for colorectal cancer may present considerable cardiovascular hazards, highlighting the necessity for routine cardiac monitoring prior to and throughout treatment. This systematic review promotes collaborative cardio-oncology strategies to reduce risk and enhance therapeutic safety.