2014年6月30日,第三期临床试验表明，TAS-102能提高全面提高结肠癌患者的存活率，这些患者的结肠癌已经转移，用普通治疗方法难以治疗。
TAS-102是一种新型的抗癌的核苷类药物，它含有三氟胸苷（trifluridine, FTD）和地匹福林盐酸盐(tipiracil hydrochloride, TPI)。其中，三氟胸苷是TAS-102的活性组成部分，能够直接和癌症的DNA互相作用，使得DNA不能正常行使功能。但是三氟胸苷口服会被大量降解为非活性状态，地匹福林盐酸盐则防止了它的降解。TAS-102的作用机理与氟嘧啶、奥沙利铂和依立替康都不同，在二期临床试验中，结果表明TAS-102对于以上三种药物都不能有效治疗的结肠癌患者有着不同的疗效。
这项研究结果可能会给转移性结肠癌患者带来希望，并且可能会被用于结肠癌患者的早期治疗，治疗可能会配合奥沙利铂或依立替康同时使用。该研究表明TAS-102的前景十分光明。

TAS-102 Extends Survival in Heavily Pretreated Colorectal Cancer
Treatment with the investigational oral agent TAS-102 significantly improved overall survival (OS) in a phase III trial for patients with heavily pretreated metastatic colorectal cancer (mCRC), prompting Taiho Oncology, the company developing the drug, to prepare a New Drug Application (NDA) for submission to the FDA.
In the phase III trial, labeled RECOURSE, approximately 800 patients with mCRC were randomized to receive best supportive care with or without the novel nucleoside TAS-102. Patients in the trial had received a median of two prior therapies. The primary outcome measure was OS with secondary endpoints focused on progression-free survival (PFS) and safety. Full data from the study will be presented at the 2014 ESMO World Conference on GI Cancer in June.
"We are very pleased by the results from the phase III RECOURSE trial in refractory mCRC, which support TAS-102 as a potential new treatment option for this patient population," Fabio M. Benedetti, MD, senior vice president and chief medical officer at Taiho Oncology, said in a press release. "The Taiho Oncology team is preparing for the submission of the NDA and [marketing authorization application] MAA of TAS-102 in the United States and the European Union, respectively."
Prior to RECOURSE, TAS-102 demonstrated promising findings and a manageable safety profile in a randomized phase II study that was published in the Lancet Oncology in October 2012. This study randomized 169 patients with heavily pretreated mCRC in a 2:1 ratio to receive TAS-102 (n = 112) or placebo (n = 57). In both the phase II and III trials, TAS-102 was administered at 35 mg/m2.
In the phase II study, the median OS was 9.0 months with TAS-102 compared with 6.6 months with placebo (HR = 0.56; 95% CI, 0.39-0.81; P = .0011). The median PFS was 2.0 months with TAS-102 compared with 1.0 month with placebo (HR = 0.41; 95% CI, 0.28-0.59; P < .0001).
In patients with wild-type KRAS tumors, the median OS with TAS-102 was 7.2 months compared with 7.0 months with placebo (P = .191). In patients with KRAS-mutant tumors, the median OS was 13.0 months with TAS-102 compared with 6.9 months for placebo (P = .0056).
Serious adverse events occurred in 19% of patients treated with TAS-102 compared with 9% of patients in the placebo arm. The most common grade 3/4 adverse events experienced with TAS-102 were neutropenia (50%), leucopenia (28%), and anemia (17%). Serious neutropenia and leucopenia did not occur in the placebo arm and grade 3/4 anemia occurred in 5% of patients receiving placebo.
TAS-102 is a novel nucleoside consisting of the cytotoxic agent trifluorothymidine (FTD) and the thymidine phosphorylase inhibitor tipiracil hydrochloride. Following the administration of treatment, FTD is phosphorylated into the DNA by thymidine kinase 1 (TK1), preventing the formation of new cancer cells.
An analysis of the prognostic qualities of TK1 in patients with mCRC treated with TAS-102 was explored in an analysis of the phase II data that were presented at the 2013 European Cancer Congress. This study looked specifically at 150 patients who underwent immunohistochemical analysis for TK1.
Overall, this study demonstrated a correlation between high-levels of TK1 expression and improved outcomes. In the TAS-102 arm, the median OS in TK1-high patients (n = 27) was 10.4 months versus 7.7 months in TK1-low patients (n = 72; HR = 0.51; 95% CI, 0.27–0.97). In the placebo arm, TK1-high patients (n = 13) had a median OS of 4.9 months compared with 7.2 months in TK1-low patients (n = 38). When applied to the entire population, the HR for OS in TK1-high patients was 0.14 (P = .0013). In TK1-low patients, the HR was 0.62 (P = .044).
In addition to CRC, TAS-102 is being explored in patients with other advanced solid tumors. A phase I study being conducted by Memorial Sloan Kettering Cancer Center is exploring TAS-102 in combination with irinotecan for patients with advanced gastrointestinal tumors (NCT01916447). This dose-finding study hopes to enroll 54 patients.
原始来源：http://news.medlive.cn/cancer/info-progress/show-62216_53.html
新抗癌组合片（三氟胸苷-Chipirashiru盐酸盐/通用名“T15·T20 Ronsafu（R）的组合片）是2014年日本获批上市治疗大肠癌患者重量级新药
【药品名称】Ronsafu（R）组合片剂T15，Ronsafu（R）的组合片剂T20
【通用名称】三氟胸苷-Chipirashiru盐酸盐
【功效】治疗不能手术切除的晚期或复发大肠癌
【用法用量】
成人每次一片，每日二次，早饭后和晚饭后， 服用2天后休息，在连续5天口服。重复此两次后， 休息14天。为1个疗程。 另外，需要的患者的状况用药。
【包装规格】
T15组合片剂：60片（2×30片） 20片（10片×2）
T20组合片剂：60片（2×30片） 20片（10片×2）
【製造商】大鵬薬品工業株式会社