Cancer therapy by docetaxel and granulocyte colony-stimulating factor (g-csf)

A method for determining optimal therapeutic regimen for the treatment of cancer with docetaxel in combination with Granulocyte Colony-Stimulating Factor (G-CSF) or pegylated Granulocyte Colony-Stimulating Factor (peg G-CSF) comprising:

• obtaining data to determine a docetaxel computer model for pharmacodynamics and pharmacokinetics of docetaxel based upon effects of docetaxel administration in vitro and/or in vivo;
• creating a docetaxel/granulopoiesis computer model to predict an optimum treatment regimen for cancer by combination of the docetaxel computer model and granulopoiesis computer model;
• determining the optimal therapeutic regimen from the one or more treatment schedules by comparing results of the computer simulations from the docetaxel/granulopoiesis computer model for reduced docetaxel-induced toxicity;
• wherein the optimal therapeutic regimen comprises administration of docetaxel in combination with G-CSF or pegylated G-CSF.

A method of determining an optimal therapeutic regimen forthe treatment of cancer with docetaxel comprising:

• obtaining data to determine a docetaxel computer model for pharmacodynamics and pharmacokinetics of docetaxel based upon effects of docetaxel administration in vitro or in vivo;
• obtaining data to determine a granulopoiesis computer model based upon measurement of neutrophils wherein the granulopoiesis computer model includes a process model for cells involved in neutrophil lineage;
• creating a docetaxel/granulopoiesis computer model to predict an optimum treatment regimen for cancer by combination of the docetaxel computer model and granulopoiesis computer model;
• performing in vitro or in vivo studies in which at least a single dose of docetaxel is administered and the in vitro or in vivo studies;
• adjusting the docetaxel/granulopoiesis computer model based on comparison of results of the in vitro or in vivo studies and computer simulations using the docetaxel/granulopoiesis computer model;
• determining one or more treatment schedules with docetaxel by the docetaxel/granulopoiesis model based upon results of computer simulations from the docetaxel/granulopoiesis computer model for docetaxel-induced toxicity;
• and
• determining an optimal therapeutic regimen with docetaxel from the one or more treatment schedules by comparing results of computer simulations from the docetaxel/granulopoiesis computer model for reduced docetaxel-induced toxicity between the one or more treatment schedules.

A method for determining optimal therapeutic regimen for the treatment of cancer with docetaxel in combination with Granulocyte Colony-Stimulating Factor (G-CSF) or pegylated Granulocyte Colony-Stimulating Factor (G-CSF) comprising:

• obtaining data to determine a docetaxel computer model for pharmacodynamics and pharmacokinetics of docetaxel based upon effects of docetaxel administration in vitro or in vivo;
• obtaining data to determine a granulopoiesis computer model based upon measurement of neutrophils wherein the granulopoiesis computer model includes a process model for cells involved in neutrophil lineage;
• wherein the granulopoiesis computer model is adjusted based on comparison of results of in vitro or in vivo post-docetaxel administration of at least a single dose of G-CSF or pegylated G-CSF performed;
• creating a docetaxel/granulopoiesis computer model to predict an optimum treatment regimen for cancer by combination of the docetaxel computer model and granulopoiesis computer model;
• performing in vitro or in vivo studies in which at least a single dose of docetaxel is administered and the in vitro or in vivo studies;
• adjusting the docetaxel/granulopoiesis model computer based on comparison of results of the in vitro or in vivo studies and computer simulations using the docetaxel/granulopoiesis computer model;
• determining one or more treatment schedules with docetaxel and G-CSF or pegylated G-CSF using the docetaxel/granulopoiesis computer model based upon results of computer simulations from the docetaxel/granulopoiesis computer model for docetaxel-induced toxicity;
• and
• determining the optimal therapeutic regimen from the one or more treatment schedules by comparing results of the computer simulations from the docetaxel/granulopoiesis computer model for reduced docetaxel-induced toxicity.

A system for optimizing a therapeutic regimen for the treatment of cancer with docetaxel, the system comprising:

• a docetaxel computer model for pharmacodynamics and pharmacokinetics of docetaxel based upon effects of docetaxel administration in vitro or in vivo;
• a granulopoiesis computer model that includes a process model for cells involved in neutrophil lineage;
• a system model modifier wherein the system model modifier is adapted to modify the neutrophil lineage based on parameters specific to an individual to generate a modified system model;
• wherein the parameters are determined from factors that may affect the pharmacokinetics of docetaxel schedule, G-CSF schedule, or pegylated G-CSF schedule;
• wherein the system is operable to account for docetaxel-induced toxicity;
• wherein the granulopoiesis model is adjusted based on comparison of results of post-docetaxel administration of at least a single dose of G-CSF or pegylated G-CSF in vitro or in vivo performed.

A system for optimizing a therapeutic regimen of docetaxel in combination of Granulocyte Colony-Stimulating Factor (G-CSF) or pegylated Granulocyte Colony-Stimulating Factor (G-CSF) for the treatment of cancer, the system comprising:

• a docetaxel computer model for pharmacodynamics and pharmacokinetics of docetaxel based upon effects of docetaxel administration in vitro or in vivo;
• a granulopoiesis computer model based upon measurement of neutrophils wherein the granulopoiesis computer model includes a process model for cells involved in neutrophil lineage;
• a system model modifier wherein the system model modifier is adapted to modify the neutrophil lineage based on parameters specific to an individual to generate a modified system model;
• wherein the parameters are determined from factors that may affect the pharmacokinetics of docetaxel or G-CSF or pegylated G-CSF schedules;
• wherein the system is operable to account for docetaxel-induced toxicity;
• wherein the granulopoiesis computer model is adjusted based on comparison of results of in vitro or in vivo post-docetaxel administration of at least a single dose of G-CSF or pegylated G-CSF.