Pharmacologic Pitfalls in the Human Tumor Clonogenic Assay

Abstract

The human tumor clonogenic assay (HTCA) (Hamburger and Salmon 1977; Salmon et al. 1978) has proved to be a useful system for screening new chemical compounds for anticancer activity (Salmon 1980; Shoemaker et al. 1983), for testing new clinical agents for phase II activity (Salmon et al. 1981; Von Hoff et al. 1981; Alberts et al. 1981a), and for predicting clinical response to cytotoxic therapy in cancer patients (Salmon et al. 1978; Alberts et al. 1980a, 1981a; Salmon et al. 1980; Salmon and Von Hoff 1981; Von Hoff et al. 1983). Despite its widespread use, additional biological and pharmacologic studies are essential before the HTCA can be considered optimized for routine clinical and laboratory research applications (Alberts et al. 1981b; Selby et al. 1983). We have previously reported suggestions for improving drug sensitivity assay conditions (Alberts et al. 1980b, 1981b), and in this presentation will discuss more recent data concerning the evaluation of (a) in vitro drug stability; (b) drug combinations which are additive in their antitumor activity; and (c) cyclophosphamide biotransformation and the relative activity of its major metabolites and a new oxazaphosphorine analog (Asta-Werke Z7557).

This work was supported in part by grants CA 17094, CA 21839, and CA 23074 from The National Institutes of Health, Bethesda, MD 20205, USA