title: miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial.
abstract: BACKGROUND
  Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach.
  
  
  METHODS
  This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels.
  
  
  RESULTS
  17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues.
  
  
  CONCLUSIONS
  Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy.
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Khurum
authors: K
authors: Khan
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: David
authors: D
authors: Cunningham
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Clare
authors: C
authors: Peckitt
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Sarah
authors: S
authors: Barton
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Diana
authors: D
authors: Tait
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.|CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Oxford, UK.
authors: Maria
authors: M
authors: Hawkins
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: David
authors: D
authors: Watkins
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Naureen
authors: N
authors: Starling
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Sheela
authors: S
authors: Rao
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Ruwaida
authors: R
authors: Begum
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Janet
authors: J
authors: Thomas
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Jacqui
authors: J
authors: Oates
authors: Department of Medicine, University of Padua, Padua, IT.
authors: Vincenza
authors: V
authors: Guzzardo
authors: Department of Medicine, University of Padua, Padua, IT.
authors: Matteo
authors: M
authors: Fassan
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.|Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK.
authors: Chiara
authors: C
authors: Braconi
authors: Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Ian
authors: I
authors: Chau
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000401:mortality / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D005641:Tegafur; D014498:Uracil; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D000069287:Capecitabine; D000068818:Cetuximab; D000093542:Gemcitabine
keywords: cetuximab; chemo-radiotherapy; miR-21; microRNA; pancreatic cancer