Author(s): Kawamura H, Ikeda K, Takiyama I, Terashima M
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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.
This article was published in Eur J Cancer
and referenced in Journal of Clinical & Experimental Pharmacology