3D radiotheraphy can be safely combined with sandwich systemic gemcitabine chemotheraphy in the management of pancreatic cancer: factors influencing outcome

Copyright © 2008 Elsevier Inc. All rights reserved.PurposeThe aim of this Phase II study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer.Methods and materialsPatients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks.ResultsFor the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (R1 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p ConclusionsThis three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial.Nigel Spry, Jennifer Harvey, Craig MacLeod, Martin Borg, Samuel Y. Ngan, Jeremy L. Millar, Peter Graham, Yvonne Zissiadis, Andrew Kneebone, Susan Carroll, Terri Davies, William H.H. Reece, Barry Iacopetta and David Goldsteinhttp://www.elsevier.com/wps/find/journaldescription.cws_home/525471/description#descriptio