1月4日,，OncoGenex制藥公司宣布Custirsen (OGX-011/TV-1011)對非小細胞肺癌的臨床研究結(jié)果,，相關研究論文在線發(fā)布于2012年1月版的《胸部腫瘤雜志》J Thorac Oncol雜志上。
Custirsen是為抑制叢生蛋白生成而被研制出的藥物,，副反應輕,，常見的為流感樣癥狀,。而叢生蛋白作為一種細胞生存相關蛋白,，在多種惡性腫瘤中都存在過表達。
該單組試驗在北美15個研究中心進行,。研究組評價了Custirsen在進展期,、未接受過先期治療的NSCLC患者中與吉西他濱/順鉑為基礎的方案聯(lián)用的療效。
研究的重要發(fā)現(xiàn)包括：1年生存率54%,，2年生存率30%,。在中位隨訪41個月（38-59個月）時，12%的患者仍存活,。31%入組患者獲得腫瘤緩解,，包括完全緩解和部分緩解,；69%患者獲得臨床緩解,，包括穩(wěn)定和客觀緩解,。中位總生存期為14.1個月,，無進展生存期為4.3個月,。
95%患者經(jīng)custirsen治療后降低了血清叢生蛋白水平。而且,，血清叢生蛋白水平≤45mcg.mL的患者中位生存期為27.1個月，而高于此水平的患者為15.6個月,。
本研究得到的生存數(shù)據(jù)與已發(fā)表的應用類似劑量的吉西他濱/順鉑為基礎的治療方案得到的7~11個月的中位總生存相比更具優(yōu)勢,。另外，Custirsen與GP方案聯(lián)用的副作用與之前報道的GP兩藥聯(lián)用的副作用相比沒有顯著差異,。
OncoGenex和Teva兩家公司今年正在計劃進行一項Custirsen應用于NSCLC的III期臨床試驗,。（生物谷bioon.com）
doi:10.1097/JTO.0b013e31823f459c
PMC:
PMID:
Phase I/II Trial of Custirsen (OGX-011), an Inhibitor of Clusterin, in Combination with a Gemcitabine and Platinum Regimen in Patients with Previously Untreated Advanced Non-small Cell Lung Cancer.
Laskin JJ, Nicholas G, Lee C, Gitlitz B, Vincent M, Cormier Y, Stephenson J, Ung Y, Sanborn R, Pressnail B, Nugent F, Nemunaitis J, Gleave ME, Murray N, Hao D.
PURPOSE:
Clusterin (CLU), an antiapoptotic, stress-associated protein, confers resistance to therapy when overexpressed. This trial tested custirsen (OGX-011), an inhibitor of CLU protein production, combined with gemcitabine/platinum in patients with advanced non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS:
This was a single-arm, multicenter, phase I/II study in chemotherapy-naive stage IIIB/IV NSCLC. Custirsen was infused during a loading dose period and weekly in combination with gemcitabine (1250 mg/m) on days 1 and 8 and with cisplatin (75 mg/m) or carboplatin (area under the curve 5) on day 1 of each 21-day cycle. Ten patients were treated in a phase I lead-in and 71 in the phase II component. The primary efficacy endpoint was response rate, with exploratory analyses of other efficacy outcomes and biomarker relationships.
RESULTS:
Eighty-one patients received custirsen and were included in the primary analysis. The median age was 61 years; 82% had stage IV disease. Overall response was 25 of 81 (31%; 95% confidence interval 21-42). The 1- and 2-year survivals were 54 and 30%, respectively. Toxicity of the combination was not appreciably different from what is reported for gemcitabine/platinum combinations. Custirsen treatment decreased serum CLU levels in 95% of patients evaluated. Patients who achieved a minimum median CLU level for the population of ≤38 μg/ml during treatment had a median survival of 27.1 compared with 16.1 months for patients who did not (p = 0.02).
CONCLUSION:
Based on the above results, a randomized phase 3 trial to evaluate the survival benefit of custirsen in patients with NSCLC is warranted.
