Testing chemotherapeutic combinations in the Human Tumor Colony--Forming Assay

A total of 362 tumor specimens were tested in the Human Tumor Colony--Forming Assay for sensitivity to one of eight drug combinations and to each component drug as a single agent. Peak pharmacologically achievable concentrations of drug were used in continuous exposure. In 175 assays greater than 50% inhibition of colony formation, defined as in vitro sensitivity, was observed for at least one drug. The percent inhibition of the most active single agent closely approximated the percent inhibition of the combination. This relationship was maintained for all tumor types and combinations tested. Resistance in vitro to each drug in a combination predicted resistance to the combination. However, our data suggest that the higher activity of combination chemotherapy relative to single agents is due to an increased probability of finding an agent to which the tumor is sensitive, rather than to a synergistic interaction between drugs.