Assessing sensitivity in suspension to cytosine arabinoside: statistical analysis, associations with clinical outcome and experimental design.
As part of the treatment protocol in 40 leukaemia patients using cytosine arabinoside for remission induction therapy, the sensitivity of each patient's blast cell progenitors to the drug was determined by the liquid suspension assay. To summarize the dose-response curves obtained in this assay, we considered a model that assumes the existence of a resistant subpopulation of progenitor cells. We also considered the median effect model popular in pharmacokinetics. Both models were similar in their ability to describe the data. Parameter values that characterize a low baseline number of progenitor cells exhibiting high sensitivity both at low and high dosages were found to indicate good prognosis. We also identified a simple, economical, robust and efficient design for conducting future assays.
Minkin
S
S
Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada.
Chow
A
A
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D016015:Logistic Models; D008954:Models, Biological; D011379:Prognosis; D012074:Remission Induction; D012107:Research Design; D016019:Survival Analysis; D014410:Tumor Stem Cell Assay / Q000706:statistics & numerical data*
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine