Not so much between the lines, incy is imo saying that they are hoping to demo both a favorable effect re. loop-back in inflammatory cancers and a direct effect on the cancer itself. It's not difficult to imagine a signal related to cachexia. And, if you think from this direction (the abstract) and focus on jak1, you'd be looking at interferons......
Pancreas. 2013 Jul;42(5):813-8. doi: 10.1097/MPA.0b013e318279b87f.
Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease.
Wu C, Fernandez SA, Criswell T, Chidiac TA, Guttridge D, Villalona-Calero M, Bekaii-Saab TS.
Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research, Institute, Columbus, OH, USA.
OBJECTIVES:
Etanercept blocks tumor necrosis factor a (TNF-a), 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 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-a, IL-1ß, IL-6, interferon-?, IL-10, and NF-?ß 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%-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.
CONCLUSIONS:
Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer. |
