Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research, Institute, Columbus, OH, USA.
Pancreas. 2013 Jul;42(5):813-8. doi: 10.1097/MPA.0b013e318279b87f.
Etanercept blocks tumor necrosis factor α (TNF-α), a proinflammatory cytokine that plays a role in cancer-related cachexia and tumor growth. A phase I/II study was conducted to assess the tolerability and efficacy of gemcitabine and etanercept in advanced pancreatic cancer.
Twenty-five patients received etanercept 25 mg subcutaneously twice weekly with gemcitabine. A control cohort of 8 patients received gemcitabine alone. The primary end point was progression-free survival at 6 months. Blood specimens were analyzed for TNF-α, IL-1β, IL-6, interferon-γ, IL-10, and NF-κβ activation. The trial is registered with ClinicalTrials.gov, number NCT00201838.
Thirty-eight patients participated in this study. In the gemcitabine-etanercept cohort, grade 3/4 drug-related toxicities included leucopenia (3) and neutropenia (6). There were 3 (12%) patients with partial response and 8 (32%) patients with stable disease. The rate of progression-free survival at 6 months was 28% [n = 7; 95% confidence interval (CI), 20%-36%]. Median time to progression was 2.23 months (95% CI, 1.86-4.36 months) and median overall survival was 5.43 months (95% CI, 3.30-10.23 months). Clinical benefit rate was 33% of the evaluable patients. A correlation was seen between IL-10 levels and clinical benefit.
Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer.
依那西普可阻断肿瘤坏死因子-α（TNF-α），后者是一种促炎细胞因子，在癌症相关性恶病质和肿瘤生长中发挥作用。一项 I/II 期研究旨在评估吉西他滨联合依那西普治疗晚期胰腺癌的耐受性和疗效。
25 例患者接受依那西普 25 mg 皮下注射，每周 2 次，联合吉西他滨；对照组 8 例患者接受吉西他滨单药治疗。主要终点为 6 个月时的无进展生存期。分析血液标本中的 TNF-α、IL-1β、IL-6、干扰素-γ、IL-10 和 NF-κβ 激活情况。本试验在 ClinicalTrials.gov 注册，编号为 NCT00201838。
共 38 例患者参与本研究。在吉西他滨联合依那西普组，3 级/4 级药物相关毒性包括白细胞减少（3 例）和中性粒细胞减少（6 例）。有 3 例（12%）患者部分缓解，8 例（32%）患者疾病稳定。6 个月时无进展生存率为 28%[n=7；95%置信区间（CI），20%-36%]。中位无进展生存期为 2.23 个月（95%CI，1.86-4.36 个月），中位总生存期为 5.43 个月（95%CI，3.30-10.23 个月）。可评价患者的临床获益率为 33%。IL-10 水平与临床获益呈相关性。
依那西普联合吉西他滨治疗安全，但并未显著增强晚期胰腺癌患者吉西他滨的疗效。
