Ochiai Takumi, Nishimura Kazuhiko, Watanabe Tomoo, Kitajima Masayuki, Hashiguchi Tadasuke, Nakatani Akinori, Marusasa Takashi, Muraki Akira, Nagaoka Isao, Futagawa Shunji
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation;
Exp Ther Med. 2010 Mar;1(2):325-329. doi: 10.3892/etm_00000050. Epub 2010 Mar 1.
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.
本研究旨在通过胶原凝胶滴包埋培养药物敏感性试验（CD-DST），确定在5-氟尿嘧啶（5-FU）中添加奥沙利铂（l-OHP）或伊立替康（SN-38）的效果，以确定在晚期结直肠癌（CRC）的个体化一线化疗中，亚叶酸钙加5-FU是否应与l-OHP（FOLFOX）或SN-38（FOLFIRI）联合使用。从24例未接受术前化疗的CRC患者中获取原发性肿瘤标本。进行CD-DST，并在多种孵育条件下获得抑制率（IR）。基于线性回归分析，针对5-FU浓度曲线下相同面积（AUC）评估添加l-OHP或SN-38的效果。5-FU与5-FU + l-OHP、5-FU与5-FU + SN-38的近似表达式及相关系数（5-FU的AUC = 72时，5-FU与5-FU + l-OHP、5-FU与5-FU + SN-38；5-FU的AUC = 144时，5-FU与5-FU + l-OHP、5-FU与5-FU + SN-38）分别为y = 0.94x + 8.53（R² = 0.95，p < 0.0004），y = 0.77x + 26.18（R² = 0.76，p < 0.0004）以及y = 0.91x + 10.90（R² = 0.94，p < 0.0004），y = 0.52x + 44.61（R² = 0.60，p < 0.0004）。5-FU与5-FU + l-OHP的近似表达式几乎符合回归线（y = x + b(1)）。这表明添加l-OHP会产生恒定的相加效应，与5-FU的IR无关。然而，5-FU与5-FU + SN-38的近似表达式符合回归线（y = ax + b(2)，a < 1，b(2)≥b(1)）。这表明由于5-FU的IR较低，添加SN-38会产生更大的相加效应。这些结果表明，对于5-FU反应不佳的患者，应选择FOLFIRI作为一线化疗方案。
