miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1746 views | HTML 1987 views | ?
Khurum Khan1, David Cunningham1, Clare Peckitt1, Sarah Barton1, Diana Tait1, Maria Hawkins1,2, David Watkins1, Naureen Starling1, Sheela Rao1, Ruwaida Begum1, Janet Thomas1, Jacqui Oates1, Vincenza Guzzardo3, Matteo Fassan3, Chiara Braconi1,4 and Ian Chau1
1 Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK
2 CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Oxford, UK
3 Department of Medicine, University of Padua, Padua, IT
4 Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK
Chiara Braconi, email:
Ian Chau, email:
Keywords: pancreatic cancer, microRNA, miR-21, chemo-radiotherapy, cetuximab
Received: November 27, 2015 Accepted: January 25, 2016 Published: February 05, 2016
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.
Patients and 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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.