Assessing the Hepatotoxic Effects of Fluoropyrimidine Chemotherapy in Male Iraqi Colorectal Cancer Patients

Abstract

Introduction: Colorectal cancer (CRC) is one the most frequently occurring cancer types among various populations. Fluoropyrimidine is the backbone of first-line chemotherapy, the oral capecitabine, or intravenous 5-fluorouracil (5-FU) in various combinations and schedules the chemotherapy regime in the treatment of a wide variety of gastrointestinal cancers. The enzyme dihydropyrimidine dehydrogenase (DPD) functions as the rate-limiting step in the metabolism of fluoropyrimidine chemotherapies, and patients with complete or partial DPD deficiency are at increased risk of severe and fatal toxicity during treatment with fluorouracil. Aim: This study aimed to examine the chemotoxicity of the 5-FU drug on hepatocytes in male Iraqi CRC patients. Materials and methods: This research is a cross-sectional study conducted between November 2022 and April 2023. The study included 80 male participants who had undergone surgical intervention for stage III CRC under the care of the Misan Health Directorate, Misan Center for Tumors Treatment, located in Misan, Iraq. Based on their subsequent surgical treatment, the participants were divided into two groups. The first group, comprising 45 males aged between 41 and 71 years, experienced a relapse despite receiving adjuvant therapy, which involved a singular cycle of fluoropyrimidine-based chemotherapy (5-FU). The second group consisted of 35 male patients with CRC, aged between 40 and 57 years, who did not experience a relapse post-adjuvant therapy. Their adjuvant therapy involved a single round of fluoropyrimidine-based chemotherapy with 5-FU. Relapse in patients was determined by assessing the white blood cell count (WBC). Results: Liver enzymes were significantly increased after 5-FU treatment, while the concentration of albumin was significantly decreased. Conclusion: The findings of our study clearly indicate that 5-FU induced hepatic injury, lowering the hepatocyte function with elevated levels of hepatic enzymes and low concentration of albumin in the blood, which is an important predictive marker of chemotherapy toxicity.