Chemosensitivity testing of docetaxel and paclitaxel for gastric cancer using the Histoculture Drug Response Assay

Abstract

4194 Background: In vitro chemosensitivity testing for individualized chemotherapy is known to improve the reponse rates although the impact on survival has not been adequately addressed. In vitro testing concentrations for new anticancer drugs such as the taxanes are unknown. Methods: Chemosensitivity tests for 30 gastric carcinoma tissues obtained at surgery were performed with Histoculture Drug Response Assay (HDRA) at 150μg/mL for 5FU and at three different concentrations for docetaxel (3, 30, 100 μg/mL) and paclitaxel (10, 60, 100 μg/mL). Inhibition rates (IR) were calculated using the formlula: (1-A/B) × 100% where A and B represent the mean absorbances of drug-treated and control wells, respectively. Results: For both drugs, the inhibition rates rose significantly as the testing concentration was elevated. Valid testing concentrations were determined as 10 μg/mL for paclitaxel and 30 μg/mL for docetaxel, based on the distribution of IRs between 0 and 100%. Five, 10 and 8 tumors were ranked as sensitive to 5FU, paclitaxel, and docetaxel, respectively. IRs of 5FU correlated significantly with those of docetaxel (R=0.37, p=0.0336), but not with those of paclitaxel, suggesting that paclitaxel may be more useful for combined or sequential administration with 5FU. Of the 30 patients, 5 underwent non-curative resection and another 5 had recurrences. Nine of these 10 patients underwent chemotherapy with S-1 (oral tegafur + Gimestat, an inhibitor of dihydroxylpyrimidine dehydrogenase), of which two patients responded, but none had been ranked as sensitive for 5FU. Two of the patients went on to receive weekly paclitaxel as a second line chemotherapy despite not being ranked as sensitive, and were found not to respond. Conclusions: Recommended concentration for HDRA was determined as 10 μg/mL for paclitaxel and 30 μg/mL for docetaxel, respectively. Correlation between the results of HDRA and clinical responses remains unclear. Given that S-1 is the most widely used front line treatment, HDRA should in future be modified to test the effect of 5FU in combination with Gimestat. No significant financial relationships to disclose.