Assessment of the Correlation Between Hypoalbuminemia and Adverse Effects of Oral Anticancer Medications in Adult Patients with Solid Tumors: A Single-Center Retrospective Cohort Study in Saudi Arabia

Background: Hypoalbuminemia is commonly seen in cancer patients. Albumin is essential in drug binding and distribution, particularly in medications with a binding affinity of ≥ 95% such as tyrosine kinase inhibitors (TKIs). However, hypoalbuminemia can cause an increase in free drug concentration of highly protein-bound drugs, which can enhance drug exposure and cause adverse events. Hypoalbuminemia can significantly affect pharmacokinetics, increasing free drug concentrations and unbound drug in plasma as a consequence of low albumin levels. These alterations in pharmacokinetics can affect patients’ tolerability to medications. The study aims to elucidate the impact of albumin levels on medication tolerability and the incidence of adverse events in adult patients with solid tumors. Methods: A retrospective cohort study was conducted of all adult patients with solid tumors receiving tyrosine kinase inhibitors (TKIs) with ≥ 95% protein binding at the Ministry of National Guards Health Affairs-affiliated hospitals, Riyadh, Saudi Arabia. Electronic medical records were reviewed to identify eligible patients initiated on TKIs between January 1, 2016 and December 31, 2022. The main outcomes of this study were survival proportions, grading adverse events, and treatment failure rates in relation to albumin levels. Results: The study included 127 patients out of 450 patients receiving 19 oral TKIs and were divided into two groups (Group A: 51.2% with hypoalbuminemia, and Group B: 48.8% without hypoalbuminemia). Results reveal a significant correlation between hypoalbuminemia and decreased survival proportions by 22% (p-value= 0.04). Additionally, the study identifies a pattern in severity of adverse events, with grade 1 being the most common. Treatment failure is observed more frequently in patients with hypoalbuminemia compared to those with normal albumin levels. Conclusion: This study conducted among a Saudi population demonstrates the critical role of serum albumin levels in predicting TKIs tolerability and treatment success in patients with solid tumors. Assessing and addressing nutritional status and serum albumin before and during TKI treatment may help clinicians identify high‑risk patients and optimize supportive care. Larger prospective studies in diverse populations are needed to validate these findings. Keywords: hypoalbuminemia, liver disease, solid tumors, protein-bound drug, serum albumin, TKI discontinuation, TKI tolerability, tyrosine kinase inhibitor