Development of a Tumor‐Bearing Animal Model to Evaluate Chemotherapy Efficacy and Toxicity

BACKGROUND: The value of cancer therapies lies in enhancing anti-tumor efficacy while minimizing toxicity. However, these aspects are rarely studied together, often due to the challenges of modelling both within the same framework. In preclinical settings, rat models like the Dark Agouti Mammary Adenocarcinoma (DAMA) model are used to evaluate both efficacy and toxicity concurrently but are limited in duration, relying on a single dose to evaluate efficacy and toxicity outcomes. AIM: This study aimed to develop a cyclical chemotherapy model using the DAMA model to better mimic multi-cycle clinical scenarios. METHODS: Methotrexate (MTX) was administered in various dosing schedules to assess tumor control and animal welfare. RESULTS: A dose of 2 mg/kg administered once weekly provided sufficient tumor control and the longest survival (14.25 ± 2.87 days), while maintaining animal welfare and yielding an acceptable efficacy-to-toxicity ratio. Dosing frequency, rather than cumulative dose, had a greater impact on welfare, as 2 mg/kg MTX once weekly substantially affected animal welfare, whereas the total cumulative dose of 4 mg/kg MTX did not. CONCLUSION: These findings will be utilized in future studies testing interventions designed for preventing chemotherapy toxicity whilst maintaining tumor efficacy.