Intensified Doxorubicin-Based Regimen Efficacy inResidual Non-Hodgkin's Lymphoma Disease:Towards a Computationally SupportedTreatment Improvement

Abstract

Despite recent advances, treatment of patients with aggressive Non-Hodgkin'slymphoma (NHL²) has yet to be optimally designed. Notwithstanding the contribution ofmolecular treatments, intensification of chemotherapeutic regimens may still be beneficial.Hoping to aid in the design of intensified chemotherapy, we put forward a mathematicaland computational model that analyses the effect of Doxorubicin on NHL over a widerange of patho-physiological conditions. The model represents tumour growth both indiffusion-limited settings, that is, in small avascular tumours and tumour cords, and inperfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicatedthe presence of a critical regimen intensity below which treatment will fall short of tumourelimination. Taking this critical intensity into account, we compared two regimenintensification strategies: Dose escalation and regimen densification, i.e. reducing theinter-dosing interval. In the diffusion-limited setting, dose escalation was somewhat moreefficient than regimen densification. In the perfusion-limited setting, both intensificationstrategies yielded similar results. The present study coupled with a realistic myelotoxicitymodel may add insight on the optimisation of NHL intensified chemotherapy design.