Yamaue Hiroki, Tanimura Hiroshi, Kono Nobuji, Aoki Yozo, Tabuse Katsuyoshi, Uchiyama Kazuhisa, Takifuji Katsunari, Iwahashi Makoto, Tani Masaji
Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama 641-8510, Japan.
Anticancer Res. 2003 May-Jun;23(3B):2559-64.
We examined thymidine phosphorylase (TP) expression and sensitivity to anticancer drugs and compared the findings with the efficacy of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine.
Patients were enrolled in this study from January 1995 to June 1998 for stages II-III colorectal cancer with curative resection. We conducted sensitivity tests of tumor tissue to 5'-DFUR and 5-fluorouracil (5-FU) using the MTT method, and measured tumor tissue TP levels using enzyme-linked immunosorbent assay (ELISA). From 2 weeks postoperatively, the patients were given oral 5'-DFUR 800 mg/m2/day (5 days administration followed by 2 days discontinuation) for one year and they were followed for 3 years postoperatively.
Of 139 patients registered, 124 were analyzed for the present study. The median 5'-DFUR administration was 362 days and the median total dose was 245.0 g. We compared prognoses in patients with positive and negative 5-FU sensitivity test results. There was a significantly better prognosis in 5-FU sensitivity-positive patients with stage III than that in the sensitivity-negative patients (p = 0.041). We also compared prognoses in patients with positive and negative 5'-DFUR sensitivity test results. There was no significant difference in cases with a cut-off value of 50% (p = 0.055), although patients with 5'-DFUR-positive-sensitivity tended to show longer survival. Patients with stage II and higher TP levels tended to have longer survival than those with lower TP expression, but there was no significant difference between groups (p = 0.087). The prognosis of patients with 5-FU-positive sensitivity and higher TP levels, the positive group, tended to have longer survival than in the negative group, but there was no significant difference between groups (p = 0.083).
5'-DFUR sensitivity test results and TP values may predict the clinical effects of this drug in colorectal cancer.
我们检测了胸苷磷酸化酶（TP）的表达以及对抗癌药物的敏感性，并将结果与卡培他滨的中间代谢产物5'-脱氧-5-氟尿苷（5'-DFUR）的疗效进行比较。
1995年1月至1998年6月，对接受根治性切除的II - III期结直肠癌患者进行本研究。我们使用MTT法对肿瘤组织进行5'-DFUR和5-氟尿嘧啶（5-FU）敏感性测试，并使用酶联免疫吸附测定（ELISA）测量肿瘤组织TP水平。术后2周起，患者口服5'-DFUR 800 mg/m²/天（给药5天，停药2天），共一年，并在术后随访3年。
登记的139例患者中，124例纳入本研究分析。5'-DFUR的中位给药天数为362天，中位总剂量为245.0 g。我们比较了5-FU敏感性测试结果为阳性和阴性患者的预后。III期5-FU敏感性阳性患者的预后明显优于敏感性阴性患者（p = 0.041）。我们还比较了5'-DFUR敏感性测试结果为阳性和阴性患者的预后。截断值为50%时，差异无统计学意义（p = 0.055），尽管5'-DFUR敏感性阳性患者的生存期有延长趋势。II期且TP水平较高的患者生存期往往比TP表达较低的患者长，但两组间差异无统计学意义（p = 0.087）。5-FU敏感性阳性且TP水平较高的患者（阳性组）的预后往往比阴性组患者生存期长，但两组间差异无统计学意义（p = 0.083）。
5'-DFUR敏感性测试结果和TP值可能预测该药物在结直肠癌中的临床疗效。
