TY - JOUR
T1 - Disrupting cytokine signaling in pancreatic cancer
T2 - A phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease
AU - Wu, Christina
AU - Fernandez, Soledad A.
AU - Criswell, Tamara
AU - Chidiac, Tarek A.
AU - Guttridge, Denis
AU - Villalona-Calero, Miguel
AU - Bekaii-Saab, Tanios S.
PY - 2013/7
Y1 - 2013/7
N2 - Objectives: 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. Methods: Twenty-five patients received etanercept 25 mg subcutane-ously 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. Results: 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%Y36%]. 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. Conclusions: Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer.
AB - Objectives: 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. Methods: Twenty-five patients received etanercept 25 mg subcutane-ously 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. Results: 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%Y36%]. 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. Conclusions: Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer.
KW - Cancer-related cachexia
KW - Etanercept
KW - Pancreatic cancer
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U2 - 10.1097/MPA.0b013e318279b87f
DO - 10.1097/MPA.0b013e318279b87f
M3 - Article
C2 - 23429495
AN - SCOPUS:84880055051
SN - 0885-3177
VL - 42
SP - 813
EP - 818
JO - Pancreas
JF - Pancreas
IS - 5
ER -