Prevalence of uncommon side effects of 5-fluorouracil and capecitabine in Saudi patients with cancer: A cross-sectional observational study

5-Fluorouracil (5-FU) and its prodrug, capecitabine, are widely used in chemotherapy for various cancers, including colorectal, breast, and gastrointestinal malignancies. While their common toxicities are well documented, uncommon, and severe side effects, such as cardiotoxicity, neurotoxicity, and hyperammonemia-related encephalopathy, remain poorly understood, particularly in certain populations. This study aimed to investigate the prevalence and severity of these rare adverse effects in patients with cancer in Saudi Arabia. This cross-sectional observational study was conducted at King Saud University Medical City over a 2-year period and enrolled 272 patients who received 5-FU or capecitabine. Collected data included demographics, cancer type, treatment regimen, and reported adverse effects. Statistical analyses assessed the frequency, severity, and risk factors associated with uncommon toxicities. A total of 39.7% of patients experienced side effects, with neurological symptoms (39.6%) being the most common, followed by ocular (12.6%) and cardiac (11.8%) toxicities. Most adverse effects occurred during the initial chemotherapy cycles. Factors such as sex, body mass index, and cancer stage influenced toxicity risk, with capecitabine showing a stronger association with side effects than 5-FU. These findings emphasize the need for population-specific studies to improve early detection and management of rare toxicities related to 5-FU and capecitabine. Understanding the genetic and environmental contributors to adverse reactions could enhance treatment safety and efficacy in Saudi patients with cancer. Although dihydropyrimidine dehydrogenase deficiency is a recognized risk factor for severe 5-FU toxicity, routine dihydropyrimidine dehydrogenase genetic testing was not conducted in this cohort. This limitation underscores the need for further research in this area, particularly among Saudi patients.