On the MTD paradigm and optimal control for multi-drug cancer chemotherapy.
In standard chemotherapy protocols, drugs are given at maximum tolerated doses (MTD) with rest periods in between. In this paper, we briey discuss the rationale behind this therapy approach and, using as example multidrug cancer chemotherapy with a cytotoxic and cytostatic agent, show that these types of protocols are optimal in the sense of minimizing a weighted average of the number of tumor cells (taken both at the end of therapy and at intermediate times) and the total dose given if it is assumed that the tumor consists of a homogeneous population of chemotherapeutically sensitive cells. A 2-compartment linear model is used to model the pharmacokinetic equations for the drugs.
Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026-1653, USA. uledzew@siue.edu
Urszula
U
Ledzewicz
Heinz
H
Schättler
Mostafa Reisi
MR
Gahrooi
Siamak Mahmoudian
SM
Dehkordi
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004334:Drug Administration Schedule; D006801:Humans; D016014:Linear Models; D055641:Mathematical Concepts; D020714:Maximum Tolerated Dose; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011157:Population Dynamics; D049490:Systems Biology
D000970:Antineoplastic Agents