Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease.
Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease.
复制标题
破坏胰腺癌中细胞因子信号传导：晚期疾病患者中与吉西他滨联合依那他看的I/II期研究。
DOI：
10.1097/mpa.0b013e318279b87f
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发表时间：
2013-07
期刊：
影响因子：
2.9
通讯作者：
Bekaii-Saab TS
中科院分区：
文献类型：
--
作者：
Wu C;Fernandez SA;Criswell T;Chidiac TA;Guttridge D;Villalona-Calero M;Bekaii-Saab TS
Etanercept blocks tumor necrosis factor-α (TNF), 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 25mg subcutaneously twice-weekly with gemcitabine. A control cohort of 8 patients received gemcitabine alone. The primary end-point was progression-free survival (PFS) at 6 months. Blood specimens were analyzed for TNF, IL-1b, IL-6, interferon-γ, IL-10, and NF-kB 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 PFS at 6 months was 28% (n=7; 95% 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.
