title: Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease.
abstract: OBJECTIVE
  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 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.
  
  
  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.
authors: Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research, Institute, Columbus, OH, USA.
authors: Christina
authors: C
authors: Wu
authors: Soledad A
authors: SA
authors: Fernandez
authors: Tamara
authors: T
authors: Criswell
authors: Tarek A
authors: TA
authors: Chidiac
authors: Denis
authors: D
authors: Guttridge
authors: Miguel
authors: M
authors: Villalona-Calero
authors: Tanios S
authors: TS
authors: Bekaii-Saab
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000068800:Etanercept; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003841:Deoxycytidine; D016753:Interleukin-10; D007371:Interferon-gamma; D000068800:Etanercept; D000093542:Gemcitabine