2012年8月28日 訊 /生物谷BIOON/ --一種新的治療那些已經(jīng)耐受或對標準治療無響應的晚期大腸癌患者的藥物給患者帶來了新的希望，相關研究論文發(fā)表在Lancet Oncology 雜志上,。
該新藥物叫TAS-102,，這項研究將藥物對169例日本不能手術的轉移性大腸癌患者進行了測試。這些病人已經(jīng)經(jīng)歷了幾輪的標準化療，但沒有效果或已經(jīng)對標準藥物治療（包括伊立替康,、奧沙利鉑,、氟尿嘧啶等藥物）出現(xiàn)了耐受。
研究人員發(fā)現(xiàn),，與安慰劑組相比,，接受TAS-102治療的患者生存時間延長，死亡風險降低,，疾病總體控制情況更好,，新藥的上述效果使得研究人員希望這種藥物可能有一天能成為一種有效的晚期不能手術的結直腸癌患者治療藥物。接受TAS-102治療的患者的中位總生存期為9個月,，而安慰劑組僅為6.6個月,。
接受TAS-102治療的患者出現(xiàn)死亡的風險比那些服用安慰劑的患者少了44％。更重要的是,，TAS-102似乎是相對安全的,，大多數(shù)患者對其耐受性良好,。雖然有些病人服用藥物后出現(xiàn)不良反應（主要是血液系統(tǒng)疾?。?/p>
據(jù)Takayuki Yoshino博士表示：大腸癌占所有癌癥病例的10％左右,，是全球癌癥相關死亡的第四大原因,。目前有沒有經(jīng)過臨床驗證的治療方案來徹底治療那些不能手術的結直腸癌患者。該研究結果顯示,，TAS-102是一個有前途的,、易于服用的安全性藥物。（生物谷：Bioon.com）
doi:10.1016/S1470-2045(12)70345-5
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PMID:
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.
