BACKGROUND: Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer. METHODS: The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1,000 mg/m(2) over 100 minutes, cisplatin 35 mg/m(2) I.V. on days 1 and 8, and celecoxib continuously at a daily dose of 800 mg. Cycles were repeated every 21 days. RESULTS: Twenty-two patients with metastatic pancreas cancer were enrolled (median age, 59.5 years; M:F, 13:9). The median number of cycles was 2 per patient. The median survival time was 5.8 months (90% CI, 3.6-7.6 months). The probability of survival at 6 months was 46% (90% CI, 27-62%). The major toxicity was neutropenia with grade 3 or 4 toxicities seen in 65% of patients. CONCLUSIONS: The addition of celecoxib to gemcitabine (by FDR) and cisplatin did not appear to increase activity of the chemotherapy doublet in patients with advanced pancreatic cancer. Celecoxib alone may not be sufficient to sensitize pancreatic cancer to the effects of conventional cytotoxic therapy.
BACKGROUND:Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer. METHODS: The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1,000 mg/m(2) over 100 minutes, cisplatin 35 mg/m(2) I.V. on days 1 and 8, and celecoxib continuously at a daily dose of 800 mg. Cycles were repeated every 21 days. RESULTS: Twenty-two patients with metastatic pancreas cancer were enrolled (median age, 59.5 years; M:F, 13:9). The median number of cycles was 2 per patient. The median survival time was 5.8 months (90% CI, 3.6-7.6 months). The probability of survival at 6 months was 46% (90% CI, 27-62%). The major toxicity was neutropenia with grade 3 or 4 toxicities seen in 65% of patients. CONCLUSIONS: The addition of celecoxib to gemcitabine (by FDR) and cisplatin did not appear to increase activity of the chemotherapy doublet in patients with advanced pancreatic cancer. Celecoxib alone may not be sufficient to sensitize pancreatic cancer to the effects of conventional cytotoxic therapy.
Authors: F E Silverstein; G Faich; J L Goldstein; L S Simon; T Pincus; A Whelton; R Makuch; G Eisen; N M Agrawal; W F Stenson; A M Burr; W W Zhao; J D Kent; J B Lefkowith; K M Verburg; G S Geis Journal: JAMA Date: 2000-09-13 Impact factor: 56.272
Authors: P A Philip; M M Zalupski; V K Vaitkevicius; P Arlauskas; R Chaplen; L K Heilbrun; V Adsay; D Weaver; A F Shields Journal: Cancer Date: 2001-08-01 Impact factor: 6.860
Authors: Ahmedin Jemal; Ram C Tiwari; Taylor Murray; Asma Ghafoor; Alicia Samuels; Elizabeth Ward; Eric J Feuer; Michael J Thun Journal: CA Cancer J Clin Date: 2004 Jan-Feb Impact factor: 508.702
Authors: Margaret Tempero; William Plunkett; Veronique Ruiz Van Haperen; John Hainsworth; Howard Hochster; Renato Lenzi; James Abbruzzese Journal: J Clin Oncol Date: 2003-07-28 Impact factor: 44.544
Authors: Noriyuki Omura; Margaret Griffith; Audrey Vincent; Ang Li; Seung-Mo Hong; Kimberly Walter; Michael Borges; Michael Goggins Journal: Mol Cancer Res Date: 2010-06-08 Impact factor: 5.852
Authors: Amanda Kirane; Jason E Toombs; Katherine Ostapoff; Juliet G Carbon; Sara Zaknoen; Jordan Braunfeld; Roderich E Schwarz; Francis J Burrows; Rolf A Brekken Journal: Clin Cancer Res Date: 2012-07-24 Impact factor: 12.531
Authors: Imtiyaz Murtaza; Mohammad Saleem; Vaqar Mustafa Adhami; Bilal Bin Hafeez; Hasan Mukhtar Journal: Cancer Res Date: 2009-01-27 Impact factor: 12.701
Authors: Chantale Charo; Vijaykumar Holla; Thiruvengadam Arumugam; Rosa Hwang; Peiying Yang; Raymond N Dubois; David G Menter; Craig D Logsdon; Vijaya Ramachandran Journal: Pancreas Date: 2013-04 Impact factor: 3.327
Authors: Jennifer Kl Colby; Russell D Klein; Mark J McArthur; Claudio J Conti; Kaoru Kiguchi; Toru Kawamoto; Penny K Riggs; Amy I Pavone; Janet Sawicki; Susan M Fischer Journal: Neoplasia Date: 2008-08 Impact factor: 5.715