Lancet Oncol：新药TAS-102治疗晚期大肠癌效果较好

一种新的治疗那些已经耐受或对标准治疗无响应的晚期大肠癌患者的药物给患者带来了新的希望，相关研究论文发表在Lancet Oncology 杂志上。

该新药物叫TAS-102，这项研究将药物对169例日本不能手术的转移性大肠癌患者进行了测试。这些病人已​​经经历了几轮的标准化疗，但没有效果或已经对标准药物治疗（包括伊立替康、奥沙利铂、氟尿嘧啶等药物）出现了耐受。

研究人员发现，与安慰剂组相比，接受TAS-102治疗的患者生存时间延长，死亡风险降低，疾病总体控制情况更好，新药的上述效果使得研究人员希望这种药物可能有一天能成为一种有效的晚期不能手术的结直肠癌患者治疗药物。接受TAS-102治疗的患者的中位总生存期为9个月，而安慰剂组仅为6.6个月。

接受TAS-102治疗的患者出现死亡的风险比那些服用安慰剂的患者少了44％。更重要的是，TAS-102似乎是相对安全的，大多数患者对其耐受性良好。虽然有些病人服用药物后出现不良反应（主要是血液系统疾病）。

据Takayuki Yoshino博士表示：大肠癌占所有癌症病例的10％左右，是全球癌症相关死亡的第四大原因。目前有没有经过临床验证的治疗方案来彻底治疗那些不能手术的结直肠癌患者。该研究结果显示，TAS-102是一个有前途的、易于服用的安全性药物。

doi:10.1016/S1470-2045(12)70345-5
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TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial

Dr Takayuki Yoshino MD a , Nobuyuki Mizunuma MD b, Kentaro Yamazaki MD c, Tomohiro Nishina MD d, Yoshito Komatsu MD e, Prof Hideo Baba MD f, Akihito Tsuji MD g, Kensei Yamaguchi MD h, Kei Muro MD i, Naotoshi Sugimoto MD j, Yasushi Tsuji MD k, Toshikazu Moriwaki MD l, Taito Esaki MD m, Prof Chikuma Hamada PhD n, Takanori Tanase MSc o, Atsushi Ohtsu MD

Background

Treatments that confer survival benefit are needed in patients with heavily pretreated metastatic colorectal cancer. The aim of this trial was to investigate the efficacy and safety of TAS-102—a novel oral nucleoside antitumour agent.

Methods

Between August 25, 2009, and April 12, 2010, we undertook a multicentre, double-blind, randomised, placebo-controlled phase 2 trial in Japan. Eligible patients were 20 years or older; had confirmed colorectal adenocarcinoma; had a treatment history of two or more regimens of standard chemotherapy; and were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin. Patients had to be able to take oral drugs; have measurable lesions; have an Eastern Cooperative Oncology Group performance status of between 0 and 2; and have adequate bone-marrow, hepatic, and renal functions within 7 days of enrolment. Patients were randomly assigned (2:1) to either TAS-102 (35 mg/m2 given orally twice a day in a 28-day cycle [2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period]) or placebo; all patients received best supportive care. Randomisation was done with minimisation methods, with performance status as the allocation factor. The randomisation sequence was generated with a validated computer system by an independent team from the trial sponsor. Investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. Safety analyses were done in the per-protocol population. The study is in progress and is registered with Japan Pharmaceutical Information Center, number JapicCTI-090880.

Findings

112 patients allocated to TAS-102 and 57 allocated to placebo made up the intention-to-treat population. Median follow-up was 11·3 months (IQR 10·7—14·0). Median overall survival was 9·0 months (95% CI 7·3—11·3) in the TAS-102 group and 6·6 months (4·9—8·0) in the placebo group (hazard ratio for death 0·56, 80% CI 0·44—0·71, 95% CI 0·39—0·81; p=0·0011). 57 (50%) of 113 patients given TAS-102 in the safety population had neutropenia of grade 3 or 4, 32 (28%) leucopenia, and 19 (17%) anaemia. No patient given placebo had grade 3 or worse neutropenia or leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events occurred in 21 (19%) patients in the TAS-102 group and in five (9%) in the placebo group. No treatment-related deaths occurred.

Interpretation

TAS-102 has promising efficacy and a manageable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to standard chemotherapies.