Abstract: Simple Summary: Paclitaxel is a chemotherapy drug widely used for breast cancer, but serious side effects, such as nerve damage and low white blood cell counts, often limit its effectiveness. Currently, chemotherapy doses are based on body surface area, but this method does not consider important individual factors like muscle and fat levels, which can affect how the drug is processed. This review explores how body composition and physical activity influence paclitaxel's effects and side effects. Regular exercise may improve treatment outcomes by supporting muscle health and reducing toxicity risks. By integrating these factors into chemotherapy dosing strategies, we can move toward a more personalized approach, ensuring that each patient receives the most effective and safest treatment. This research highlights the need for further studies to refine chemotherapy dosing, potentially leading to better treatment experiences and outcomes for breast cancer patients. Background/Objectives: Paclitaxel is a type of small molecule chemotherapy widely used for breast cancer, but its clinical efficacy is often hindered by dose-limiting toxicities such as chemotherapy-induced peripheral neuropathy and neutropenia. Traditional dosing based on body surface area does not account for variations in body composition, which may influence paclitaxel metabolism, toxicity, and treatment outcomes. This review explores the interplay between body composition, physical activity, and paclitaxel pharmacokinetics, emphasizing the potential for personalized dosing strategies. Methods: A comprehensive narrative review was conducted by analyzing the literature on body composition, small molecule chemotherapy-related toxicities, pharmacokinetics, and exercise oncology. Studies examining the role of skeletal muscle mass, adipose tissue, and physical activity in modulating paclitaxel metabolism and side effects were included. Results: Evidence suggests that patients with low skeletal muscle mass are at a higher risk of paclitaxel-induced toxicities due to altered drug distribution and clearance. Sarcopenic obesity, characterized by low muscle and high-fat levels, further exacerbates these risks. Exercise, particularly resistance and aerobic training, has been shown to improve muscle mass, mitigate toxicities, and enhance chemotherapy tolerance. However, the precise mechanisms by which exercise influences paclitaxel pharmacokinetics remain underexplored. Conclusions: Personalized chemotherapy dosing, considering body composition and physical activity, may optimize paclitaxel treatment outcomes. Future research should focus on integrating exercise interventions into oncology care and refining dosing models that account for interindividual differences in drug metabolism. These advancements could improve treatment efficacy while minimizing toxicities in breast cancer patients. [ABSTRACT FROM AUTHOR]
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