Pharmacologic assessment of regimen chemosensitivity in the soft-agar assay: effect of oxygen on human tumors.

The influence of oxygen on the growth and the in vitro chemosensitivity of human tumor cells was studied in the soft-agar assay. Tumor cells of pancreatic and ovarian origin prefer a reduced oxygen atmosphere for colony formation, whereas those of pulmonary origin grow better in 20% oxygen. Depending on the physiologic oxygen tension and the histologic origin of a particular cancer type, the in vitro chemosensitivity of many drug obtained with the conventional culture system could be inadequately assessed. The in vitro responses of tumor cells to combinations of drugs were measured by the regimen efficacy index (REI) method. The REI delineates the possible regimen enhancement or regimen default based on the in vitro chemosensitivity of the individual agents tested in the assay. In vitro regimen enhancement was observed only in ascites incubated in a reduced oxygen atmosphere with two-drug combinations. However, regardless of the oxygen gradients used, regimen default was seen in cancer cells of solid tumors treated with all combinations of drugs tested. This study suggests further investigation on the effects of oxygen in the soft-agar assay, and proposes the novel use of the REI method for evaluating the in vitro regimen chemosensitivity of human tumor cells.