Intensified Doxorubicin-Based Regimen Efficacy in Residual Non-Hodgkin's Lymphoma Disease: Towards a Computationally Supported Treatment Improvement

Abstract

Abstract. Despite recent advances, treatment of patients with aggressive Non-Hodgkin's lymphoma (NHL 2 ) has yet to be optimally designed. Notwithstanding the contribution of molecular treatments, intensification of chemotherapeutic regimens may still be beneficial. Hoping to aid in the design of intensified chemotherapy, we put forward a mathematical and computational model that analyses the effect of Doxorubicin on NHL over a wide range of patho-physiological conditions. The model represents tumour growth both in diffusion-limited settings, that is, in small avascular tumours and tumour cords, and in perfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicated the presence of a critical regimen intensity below which treatment will fall short of tumour elimination. Taking this critical intensity into account, we compared two regimen intensification strategies: Dose escalation and regimen densification, i.e. reducing the inter-dosing interval. In the diffusion-limited setting, dose escalation was somewhat more efficient than regimen densification. In the perfusion-limited setting, both intensification strategies yielded similar results. The present study coupled with a realistic myelotoxicity model may add insight on the optimisation of NHL intensified chemotherapy design.

Improving Cancer Therapy by Doxorubicin and Granulocyte Colony-Stimulating Factor: Insights from a Computerized Model of Human Granulopoiesis

“…The rationale underlying dose intensification is based on dynamical considerations of tumor growth. First introduced by Goldie and Coldman in a simple logistic model of tumor cell proliferation, this concept is still valid in more complicated physiologically-based models of tumor growth [10].…”