1月4日，OncoGenex制药公司宣布Custirsen (OGX-011/TV-1011)对非小细胞肺癌的临床研究结果，相关研究论文在线发布于2012年1月版的《胸部肿瘤杂志》J Thorac Oncol杂志上。
Custirsen是为抑制丛生蛋白生成而被研制出的药物，副反应轻，常见的为流感样症状。而丛生蛋白作为一种细胞生存相关蛋白，在多种恶性肿瘤中都存在过表达。
该单组试验在北美15个研究中心进行。研究组评价了Custirsen在进展期、未接受过先期治疗的NSCLC患者中与吉西他滨/顺铂为基础的方案联用的疗效。
研究的重要发现包括：1年生存率54%，2年生存率30%。在中位随访41个月（38-59个月）时，12%的患者仍存活。31%入组患者获得肿瘤缓解，包括完全缓解和部分缓解；69%患者获得临床缓解，包括稳定和客观缓解。中位总生存期为14.1个月，无进展生存期为4.3个月。
95%患者经custirsen治疗后降低了血清丛生蛋白水平。而且，血清丛生蛋白水平≤45mcg.mL的患者中位生存期为27.1个月，而高于此水平的患者为15.6个月。
本研究得到的生存数据与已发表的应用类似剂量的吉西他滨/顺铂为基础的治疗方案得到的7~11个月的中位总生存相比更具优势。另外，Custirsen与GP方案联用的副作用与之前报道的GP两药联用的副作用相比没有显著差异。
OncoGenex和Teva两家公司今年正在计划进行一项Custirsen应用于NSCLC的III期临床试验。（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.
