Clinical application of histoculture drug response assay (HDRA) for gastrointestinal cancers with reference to cumulative efficacy rate curve

Histoculture Drug Response Assay (HDRA) with MTT-endpoint was performed using surgical specimens, including 79 gastric and 94 colorectal cancers from 17 hospitals. Surgical specimens were cut into pieces, placed onto collagen-gel-matrix in the medium containing each concentration of mitomycin C (MMC), 5-fluorouracil (5-FU), adriamycin (ADM) and cisplatin (DDP), and incubated for 7 days. At the end of incubation, the viability of tumor cells was evaluated according MTT methods, in which fifty percent or more inhibition rate at each concentration was evaluated as positive. Ninety percent gastric and ninety-three percent colorectal cancer cases were evaluable. Using the cumulative efficacy rate curve, the optimal cutoff concentrations were estimated as 2 μg/ml for MMC, 300 μg/ml for 5-FU, 15 μg/ml for ADM and 20 μg/ml for DDP. Efficacy rates obtained from these cutoff concentrations were 32.7% for MMC, 20.0% for 5-FU, 11.9% for ADM and 8.8% for DDP in gastric cancer, and 15.9% for MMC, 19.7% for 5-FU, 9.6% for ADM and 6.6% for DDP in colorectal cancer. These cutoff concentrations obtained from cumulative efficacy rate curves were essentially identical to those in our previous report. And high sensitivity to 5-FU and low sensitivity of DDP in colorectal cancer were successfully reproduced in the study. HDRA with MTT-endpoint would be useful for further clinical application.