Adaptive control of etoposide administration: impact of interpatient pharmacodynamic variability.
We sought to use a previously derived pharmacodynamic model for 72-hour etoposide infusions to adaptively control administration of this agent and to demonstrate that more predictable toxicity could be obtained with this dosing scheme. A randomized crossover study design was used to compare "standard" dosing (125 mg/m2/day) to adaptive control, with dose adjustment at 28 hours based on the 24-hour plasma level. A total of 31 patients received 86 cycles of chemotherapy, 36 by standard dosing and 50 by adaptive control. However, there was no demonstrable advantage to the adaptive control scheme, because of apparent bias of the previous model. A new model was proposed that also included serum albumin, performance status, and prior RBC transfusions as measures of interpatient pharmacodynamic variability. We conclude that adaptive control dosing of etoposide is feasible but that the therapy must be individualized for both pharmacokinetic and pharmacodynamic variability.
Ratain
M J
MJ
Lynn Sage Clinical Pharmacology Laboratory for Cancer Research, Department of Medicine, University of Chicago, Pritzker School of Medicine, IL.
Schilsky
R L
RL
Choi
K E
KE
Guarnieri
C
C
Grimmer
D
D
Vogelzang
N J
NJ
Senekjian
E
E
Liebner
M A
MA
D000465:Algorithms; D005047:Etoposide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D015233:Models, Statistical; D011897:Random Allocation
D005047:Etoposide