Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity test

Abstract

The purpose of this study was to determine the effect of the addition of oxaliplatin (l-OHP) or irinotecan (SN-38) to 5-fluorouracil (5-FU) using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to establish whether leucovorin plus 5-FU should be administered in combination with l-OHP (FOLFOX) or SN-38 (FOLFIRI) in individualized first-line chemotherapy for the treatment of advanced colorectal cancer (CRC). Specimens of primary tumors were obtained from 24 CRC patients who had received no preoperative chemotherapy. CD-DST was performed, and the inhibition rate (IR) was obtained under multiple incubation conditions. The effects of addition of l-OHP or SN-38 were evaluated for the same area under the concentration curve (AUC) of 5-FU based on linear regression analysis. Approximate expression and correlation coefficients (5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=72 and 5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=144) were y=0.94x+8.53 (R(2)=0.95, p<0.0004), y=0.77x+26.18 (R(2)=0.76, p<0.0004) and y= 0.91x+10.90 (R(2)=0.94, p<0.0004), y=0.52x+44.61 (R(2)=0.60, p<0.0004), respectively. Approximate expression of 5-FU vs. 5-FU + l-OHP almost fit the regression line (y=x+b(1)). This suggests that addition of l-OHP yields a constant additive effect, independent of the IR of 5-FU. However, approximate expression of 5-FU vs. 5-FU + SN-38 fit the regression line (y=ax+b(2), a<1, b(2)≥b(1)). This suggests that addition of SN-38 yields a greater additive effect due to the lower IR of 5-FU. These results indicate that FOLFIRI should be selected as the first-line chemotherapy for the treatment of poor responders to 5-FU.