EXPERIMENTAL-DESIGN FOR CLONOGENIC ASSAYS IN CHEMOTHERAPY

One approach to estimating the number of cells with high growth potent ial in a cancer patient is the assessment of tumor cell colony formati on in semisolid medium. A potential indicator of the clinical response to a specific drug is the capacity of the drug to reduce the formatio n of cell colonies. Often, a Poisson log-linear model provides an adeq uate representation of the dose-response curve. This model is then sum marized by the dose required to reduce the number of colonies to a pre determined percentage of the maximum growth. But more general models a re needed to account for the overdispersion and the resistant subpopul ations often present in these assays. This article explores alternativ e methods for selecting the dose levels to obtain precise estimates of the parameters of interest. Optimal dose allocations for a single pat ient or a group of patients are derived. Methods to incorporate the in formation from pilot studies are discussed. A study of drug sensitivit y with leukemia patients provides the framework and motivation for the problem.