title: 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome.
abstract: OBJECTIVE
  The 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
  Patients 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.
  
  
  RESULTS
  For 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 < 0.0001, respectively).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. Nigel.Spry@health.wa.gov.au
authors.forename: Nigel
authors.initials: N
authors.lastname: Spry
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harvey
authors.forename: Craig
authors.initials: C
authors.lastname: Macleod
authors.forename: Martin
authors.initials: M
authors.lastname: Borg
authors.forename: Samuel Y
authors.initials: SY
authors.lastname: Ngan
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Millar
authors.forename: Peter
authors.initials: P
authors.lastname: Graham
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Zissiadis
authors.forename: Andrew
authors.initials: A
authors.lastname: Kneebone
authors.forename: Susan
authors.initials: S
authors.lastname: Carroll
authors.forename: Terri
authors.initials: T
authors.lastname: Davies
authors.forename: William H H
authors.initials: WH
authors.lastname: Reece
authors.forename: Barry
authors.initials: B
authors.lastname: Iacopetta
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018395:CA-19-9 Antigen / Q000097:blood; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine