The usefulness of the ATP assay with serum-free culture for chemosensitivity testing of gastrointestinal cancer.

Abstract

In order to predict a patient's response to a drug prior to chemotherapy for gastrointestinal cancer, we developed an adenosine triphosphate (ATP) assay with serum-free culture (SF-ATPA) which enables fibroblast overgrowth to be suppressed. A total of 244 gastrointestinal cancer tissue samples were obtained from surgical resection. After enzymatic digestion, cells (2 x 10(4)/well) were cultured for 72 h with continuous exposure to drugs (single or combined use), and cell viability was evaluated by measuring the intracellular ATP level. 208 of 244 samples (85%) were considered to be evaluable in terms of drug response. There were no differences in the evaluability rates among the tumour types. A drug was judged as active using the criterion of < or = 50% reduction of the intracellular ATP level in a single-agent treated group compared with the level of the control. Similarly, in the combined drug treated group, drugs were considered as active using two different criteria (< or = 30% reduction of the intracellular ATP level for two drugs and < or = 20% for three drugs). Each tumour type had its own spectrum for chemosensitivity. Of 25 patients evaluated for assay-clinical correlations, 16 were examined by both single-agent and combined drug administration and the predictive accuracy of the assay was higher for the combined drug than for the single agent (88% versus 69%, respectively). In 25 patients, the true positive rate was 64% and the true negative rate was 100%, yielding an overall predictive accuracy of 84%. These results suggest that SF-ATPA may be useful for predicting drug response in patients with gastrointestinal cancer.