治疗结肠癌的新型药物组合

  近日，一项刊登于国际杂志New England Journal of Medicine上的研究论文中，来自美国达纳-法伯癌症研究所(Dana-Farber Cancer Institute)的研究人员通过研究发现，仅给予名为TAS-102的单一药片药物组合，就可以不仅延长转移性结直肠癌患者的生存率，而且还可以减缓患者疾病的进展，而且对患者副作用较小。
  文章中，研究者表示，大约一半转移性结直肠癌患者在进行标准化疗制剂—氟嘧啶治疗后并没有获得治疗效益，而TAS-102可以有效抑制大多数患者的病情，这或许就可以揭示这种药物组合制剂或许通过了一种异于氟嘧啶的生化途径来发挥作用给患者带来帮助。
  研究者Robert J. Mayer表示，结直肠癌是世界上常见的仅次于肺癌的第二大引发死亡的常见癌症，本文研究中我们在3期临床试验中招募了800名患转移性结直肠癌的患者进行研究，这些患者尽管之前进行过治疗，但疾病依然在发展，研究者对其随机进行TAS-102或安慰剂药片治疗。
  结果显示，安慰剂服用患者的生存中值为5.3个月，而服用TAS-102的患者则为7.1个月；研究者指出，TAS-102中杀灭癌细胞的组分为一种名为曲氟尿苷的药物，其是在20世纪50年代被开发出来的，曲氟尿苷可以整合入癌细胞的DNA，但当其以一定剂量杀灭癌细胞时其对患者也具有毒性；在大约15年前一家日本制药公司开始检测曲氟尿苷结合tipiracil盐酸盐的治疗效果，后者是一种可以阻断曲氟尿苷代谢的制剂；这种药物组合可以使得曲氟尿苷在不伤害患者机体的条件下给患者带来益处，有效潜在地杀灭癌细胞。
  这项研究中研究人员首次揭示了TAS-102对转移性结直肠癌患者的治疗效果，下一步他们将会将TAS-102同其它药物进行组合，比如结合5-氟尿嘧啶，来研究其对患者的治疗效果，研究者希望本文的研究结果为后期开发有效抑制结直肠癌患者新型疗法会带来一定的帮助。

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转化医学网推荐的原文摘要：

Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer

NEJM DOI: 10.1056/NEJMoa1414325
Robert J. Mayer, M.D., Eric Van Cutsem, M.D., Ph.D., Alfredo Falcone, M.D., Takayuki Yoshino, M.D., Rocio Garcia-Carbonero, M.D., Ph.D., Nobuyuki Mizunuma, M.D., Ph.D., Kentaro Yamazaki, M.D., Yasuhiro Shimada, M.D., Josep Tabernero, M.D., Ph.D., Yoshito Komatsu, M.D., Ph.D., Alberto Sobrero, M.D., Eveline Boucher, M.D., Marc Peeters, M.D., Ph.D., Ben Tran, M.B., B.S., Heinz-Josef Lenz, M.D., Alberto Zaniboni, M.D., Howard Hochster, M.D., James M. Cleary, M.D., Hans Prenen, M.D., Ph.D., Fabio Benedetti, M.D., Hirokazu Mizuguchi, M.S., Lukas Makris, Ph.D., Masanobu Ito, M.S., and Atsushi Ohtsu, M.D., Ph.D. for the RECOURSE Study Group
BACKGROUND
Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients.
METHODS
In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary end point was overall survival.
RESULTS
The median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for death in the TAS-102 group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically significant adverse events associated with TAS-102 were neutropenia, which occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of the patients who received TAS-102 had febrile neutropenia, and one death related to TAS-102 was reported. The median time to worsening performance status (a change in Eastern Cooperative Oncology Group performance status [on a scale of 0 to 5, with 0 indicating no symptoms and higher numbers indicating increasing degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78; P<0.001).
CONCLUSIONS
In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology–Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.)