Increasing the Time Interval between PCV Chemotherapy Cycles as a Strategy to Improve Duration of Response in Low-Grade Gliomas: Results from a Model-Based Clinical Trial Simulation

Background. We previously developed a mathematical model capturing tumor size dynamics of adult low-grade gliomas (LGGs) before and after treatment either with PCV (Procarbazine, CCNU, and Vincristine) chemotherapy alone or with radiotherapy (RT) alone. Objective. The aim of the present study was to present how the model could be used as a simulation tool to suggest more effective therapeutic strategies in LGGs. Simulations were performed to identify schedule modifications that might improve PCV chemotherapy efficacy. Methods. Virtual populations of LGG patients were generated on the basis of previously evaluated parameter distributions. Monte Carlo simulations were performed to compare treatment efficacy across in silico clinical trials. Results. Simulations predicted that RT plus PCV would be more effective in terms of duration of response than RT alone. Additional simulations suggested that, in patients treated with PCV chemotherapy, increasing the interval between treatment cycles up to 6 months from the standard 6 weeks can increase treatment efficacy. The predicted median duration of response was 4.3 years in LGGs treated with PCV cycles given every 6 months versus 3.1 years in patients treated with the classical regimen. Conclusion. The present study suggests that, in LGGs, mathematical modeling could facilitate clinical research by helping to identify, in silico, potentially more effective therapeutic strategies.