Chemotherapy may be delivered based on an integrated view of tumour dynamics.
The aim here was to explore the potential of pharmacokinetic (PK)/pharmacodynamic (PD) and physiopathological parameters in explaining the primary effects of an anti-cancer treatment that targets cells in a specific cell cycle phase. The authors applied a theoretical multi-scale disease model of tumour growth that integrates cancer processes at the cellular and tissue scales. The mathematical model at the cell level relies on a dynamic description of cell cycle regulation while the model at the tissue level is based on fluid mechanics considerations. Simulations show that the number of target cells oscillates as the tumour grows after a first cycle of chemotherapy. Both treatment effect and tumour growth processes drive these oscillations. Nonetheless, results indicate that parameters related to physiopathological processes may have greater relevance than classical drug-related parameters in determining the efficacy of a chemotherapy treatment protocol. Physiopathological parameters, in particular those related to cell cycle regulation, may be integrated in PK/PD models aimed at optimising the delivery of phase-specific cytotoxic treatments.
Ribba
B
B
Universite de Lyon, Lyon, France. Benjamin.Ribba@recherche.univ-lyon1.fr
You
B
B
Tod
M
M
Girard
P
P
Tranchand
B
B
Trillet-Lenoir
V
V
Freyer
G
G
D000465:Algorithms; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle; D003198:Computer Simulation; D006801:Humans; D055806:Microvessels / Q000503:physiopathology; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D049490:Systems Biology
D000970:Antineoplastic Agents; D010100:Oxygen