Nukatsuka M, Fujioka A, Saito H, Uchida J, Nakano K, Takeda S, Unemi N
Anticancer & Antimicrobial Research Lab., Taiho Pharmaceutical Co., Ltd. Tokushima-Shi, Japan.
Cancer Lett. 1996 Jul 12;104(2):197-203. doi: 10.1016/0304-3835(96)04247-4.
We assayed the antitumoral and anticachectic activity of an oral fluoropyrimidine, UFT using the Colon-26-bearing murine cachexia model in terms of the survival period and parameters corresponding to clinical symptoms. Tumor growth was inhibited by UFT dose-dependently at the dose range of 12.5-25.0 mg/kg per day. Although UFT did not show significant growth inhibition at 15.0 and 12.5 mg/kg to which UFT gave little toxicity, the survival period was shown to be superior to the case of maximum tolerated dose (25.0 mg/kg per day). Next, we compared the maximum increase of life span (ILS) value for an administration schedule of continuous 9 days and 5 weeks which mimics the clinical schedule and found that the ILS value in the latter group was superior to the former and UFT improved cachexia, in the same manner. In the following experiments, we have clarified that UFT decreased the level of both plasma interleukin-6 (IL-6) and tumorous prostaglandin E2 (PGE2) and it highly accelerated IL-6 production from Colon-26. These findings suggest that UFT therapy, in low-toxic dose, could be useful to cachectic patients with poor performance status.
我们使用携带Colon-26的小鼠恶病质模型,从生存期和与临床症状相关的参数方面,测定了口服氟嘧啶UFT的抗肿瘤和抗恶病质活性。在每天12.5 - 25.0 mg/kg的剂量范围内,UFT对肿瘤生长的抑制呈剂量依赖性。虽然在15.0和12.5 mg/kg时UFT未显示出显著的生长抑制,且这两个剂量的UFT毒性很小,但生存期显示优于最大耐受剂量(每天25.0 mg/kg)的情况。接下来,我们比较了模拟临床给药方案连续给药9天和5周的最大寿命延长(ILS)值,发现后一组的ILS值优于前一组,并且UFT以相同方式改善了恶病质。在接下来的实验中,我们阐明了UFT降低了血浆白细胞介素-6(IL-6)和肿瘤前列腺素E2(PGE2)的水平,并且它极大地加速了Colon-26产生IL-6。这些发现表明,低毒剂量的UFT治疗可能对身体状况较差的恶病质患者有用。