晚期结直肠癌转移患者需要的是有益于其生存的治疗。来自日本的研究者在Lancet Oncol 最新在线期刊上发表了相关研究，旨在调查一种新型口服核苷类抗肿瘤制剂TAS-102在患者中的有效性和安全性。
本研究的时间为2009年8月25日至2010年4月12日，是在日本进行的一个多中心双盲随机安慰剂对照2期临床研究。患者的入选标准为年龄大与等于20岁、已确诊为结直肠腺癌、已接受了2种或以上的标准治疗、并且对氟尿嘧啶、伊立替康、奥沙利铂等药物无效或产生耐受性。同时患者必须能接受口服给药、其病变区域可测量、美国东部肿瘤协作组评级为0至2级、入组前7天的化验显示骨髓象、肝肾功能正常。符合上述条件的患者按照2:1的比例随机分入TAS-102治疗组和对照组，治疗组的治疗方案为按照35mg/m2的剂量每日两次口服，治疗周期为28天，最初2周中，连续5天给药后停用2天，然后进入14天的休息期。两组患者都接受最好的支持治疗。研究者采用最小化方法进行随机分组。研究的资助者采用电脑生成入组的随机数列。研究者、患者、数据分析者和研究资助者皆不知道患者所接受的治疗方案。原发终点事件是意向性治疗人群中的总体生存情况。试验后对两组患者分别进行安全性分析。本研究在日本制药信息中心注册。
研究中，TAS-102治疗组纳入112名受试者而安慰剂组纳入57名受试者。研究平均随访时间为11.3月。TAS-102治疗组平均总体生存时间为9.0月而对照组为6.6月。TAS-102治疗组中50%的受试者存在3或4级中性粒细胞减少、28%存在白细胞减少、17%存在贫血。安慰剂组中没有受试者出现3级/或以上的中性粒细胞减少或白细胞减少，5%的受试者出现3级/或以上的贫血。治疗组中有19%的受试者出现严重不良反应而该数值在安慰剂组中为9%。研究未出现治疗相关的死亡事件。
研究者指出TAS-102对已经耐受或对标准治疗无反应的晚期转移性结直肠癌患者中的应用是安全且有效的。
TAS-102 Improves Survival in Advanced Colorectal Cancer
Researchers recently reported that the new combination agent TAS-102 improves overall survival in patients whose metastatic colorectal cancer is refractory to standard therapies. These results were recently reported at the ESMO 16th World Congress on Gastrointestinal Cancer in Barcelona.1
According to estimates from the American Cancer Society, more than 102,000 new cases of colon cancer and about 40,000 new cases of rectal cancer were diagnosed in the United States in 2013.2 Together, the diseases were responsible for over 50,000 deaths. There is, however, good news about colorectal cancer in the United States: death rates associated with the disease have dropped during the past 15 years, and advances continue to be made in screening, prevention, and treatment. Unfortunately many individuals will fail initial therapy and develop metastatic disease. Continued development of drugs to treat metastatic colon cancer is necessary to further improve outcomes.
TAS-102 is a novel anti-cancer agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is the active component of TAS-102 and is directly incorporated into cancer DNA, leading to DNA dysfunction. However, when FTD is taken orally it is largely degraded to an inactive form. TPI prevents the degradation of FTD. A previously reported phase II trial of TAS-102 found an overall survival benefit in Japanese patients with metastatic colorectal cancer refractory to treatment.
The current RECOURSE study was a global phase III trial conducted in 13 countries. Patients had metastatic colorectal cancer refractory to all standard therapies including with wild-type KRAS tumors. Patients were treated with TAS-102 (534 patients) or placebo (266 patients) and directly compared.
The researchers found that TAS-102 prolonged overall survival experiencing a median overall survival of 7.1 months for TAS-102 and 5.3 months for placebo. TAS-102 also improved progression-free survival and was well tolerated with the most common side-effect being neutropenia.
Reference:
1.Yoshino T, Mayer R, Falcone A, et al. Results of a multicenter, randomised, double-blind, phase III study of TAS-102 vs. placebo, with best supportive care (BSC), in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies (RECOURSE). Ann Oncol 2014 Jun; 25(Suppl 2):1-117.
2. Cancer Facts and Figures http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf Accessed March 2014.
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