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 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.
OBJECTIVES: Etanercept blocks tumornecrosis 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: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: W von Bernstorff; M Voss; S Freichel; A Schmid; I Vogel; C Jöhnk; D Henne-Bruns; B Kremer; H Kalthoff Journal: Clin Cancer Res Date: 2001-03 Impact factor: 12.531
Authors: A Trauzold; H Wermann; A Arlt; S Schütze; H Schäfer; S Oestern; C Röder; H Ungefroren; E Lampe; M Heinrich; H Walczak; H Kalthoff Journal: Oncogene Date: 2001-07-12 Impact factor: 9.867
Authors: M A Cooper; T A Fehniger; S C Turner; K S Chen; B A Ghaheri; T Ghayur; W E Carson; M A Caligiuri Journal: Blood Date: 2001-05-15 Impact factor: 22.113
Authors: John C Davis; Désirée Van Der Heijde; Jurgen Braun; Maxime Dougados; John Cush; Daniel O Clegg; Alan Kivitz; Roy Fleischmann; Robert Inman; Wayne Tsuji Journal: Arthritis Rheum Date: 2003-11
Authors: Craig L Leonardi; Jerold L Powers; Robert T Matheson; Bernard S Goffe; Ralph Zitnik; Andrea Wang; Alice B Gottlieb Journal: N Engl J Med Date: 2003-11-20 Impact factor: 91.245
Authors: Bertram Wiedenmann; Peter Malfertheiner; Helmut Friess; Paul Ritch; James Arseneau; Giovanni Mantovani; Francesco Caprioni; Eric Van Cutsem; Dirk Richel; Mark DeWitte; Ming Qi; Don Robinson; Bob Zhong; Carla De Boer; J D Lu; Uma Prabhakar; Robert Corringham; Daniel Von Hoff Journal: J Support Oncol Date: 2008-01