517P - TRUST: Phase II trial of induction chemotherapy (CT) with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) + BV and surgery in loc...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Surgical oncology
Colon and Rectal Cancer
Radiation oncology
Presenter Caterina Vivaldi
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors C. Vivaldi1, P. Buccianti2, G. Musettini3, F. Bergamo4, M.D. Rizzato4, A. Sainato5, A. Martignetti6, S. Lucchesi7, M. Franceschi2, C. Boso8, F. Pasqualetti5, L. Ginocchi7, F. Di Clemente9, A. Gonnelli5, L. Urbani10, S. Montrone5, I. Maretto11, F. Sidoti2, A. Falcone12, G. Masi1
  • 1Oncologia Medica Universitaria, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 2U.o. Chirurgia Generale, Azienda Ospedaliero Universitaria Pisana, 56100 - Pisa/IT
  • 3Medical Oncology, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 4Dipartimento Di Oncologia Clinica E Sperimentale, Uoc Oncologia Medica 1, Istituto Oncologico Veneto IRCCS, Padova/IT
  • 5U.o. Radioterapia, Azienda Ospedaliera Universitaria S.Chiara, Pisa/IT
  • 6Dh Oncologico Val D'elsa, Azienda USL Toscana sud est, Siena/IT
  • 7Department Of Oncology, Ospedale “F. Lotti” Pontedera, 56025 - Pontedera/IT
  • 8Uoc Di Radioterapia, Istituto Oncologico Veneto IRCCS, Padova/IT
  • 9Dh Oncologico Valdichiana, Azienda USL Toscana sud est, Siena/IT
  • 10U.o. Chirurgia Generale, Azienda Ospedaliera Universitaria Pisana, 56100 - Pisa/IT
  • 11Dipartimento Di Scienze Chirurgiche, Oncologiche E Gastroenterologiche, Clinica Chirurgica 1, Università di Padova, Padova/IT
  • 12Oncologia Medica Universitaria, Azienda Ospedaliera Universitaria S.Chiara, Pisa/IT



Induction CT followed by CRT is a promising strategy in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer.


This is a phase II single-arm trial. Patients (pts) with LARC at


We enrolled 48 pts: median age, 53 years (30-74); cT2/T3/T4, 4%/60%/36%; cN0/N + , 4%/96%; distance from anal verge 0-5/5-10/ > 10 cm, 56%/38%/6%. 46 pts completed induction therapy; 2 pts prematurely stopped treatment: 1 bowel perforation and sepsis resulting in death and 1 acute kidney injury recovered without sequelae. Main grade (G) 3/4 toxicities were: neutropenia (42%), febrile neutropenia (4.2%) and diarrhea (12.5%). After induction therapy 45 pts started CRT and 1 underwent surgery. After the first 13 pts, the protocol was amended and the schedule of capecitabine slightly modified (800 mg/m2/bid 5 days/week) due to an excessive rate of G3 hand-foot syndrome (23%) and proctitis (23%). After amendment, all pts completed CRT with acceptable toxicity: no G3-4 toxicities were reported, with the exception of proctitis (6.2%). After CRT 44 pts underwent surgery (1 died due to early progression after CRT): low anterior (89%) or abdomino-perineal (7%) resection. R0 resection was achieved in 98% resected pts. Early post-surgical complication rate was 32%, with a rate of 18% of anastomotic dehiscences (all solved). Pathologic complete response (pCR) rate was 36%. At a median follow up of 25.1 months, 11 pts experienced disease progression (3 local recurrences) and the estimated 2-year DFS is 78.8%.


Induction therapy with FOLFOXIRI + BV followed by CRT + BV is feasible, but a careful patient selection is needed because of the overall safety profile. Results in terms of pCR and preliminary DFS data are promising.

Clinical trial identification

EUDRACT 2011-003340-45 Start Date: 2012-02-23

Legal entity responsible for the study

Fondazione ARCO Onlus


trial promoted by Fondazione ARCO Onlus, bevacizumab provided by Roche


A. Falcone: Honoraria, advisory role, speakers' bureau: Amgen, Bayer, Merck Serono, Roche, Sanofi, Lilly. Research funding: Amgen, Bayer, Merck Serono, Roche, Sanofi. G. Masi: Honoraria: Roche, Merck Serono, Amgen, Sirtex. All other authors have declared no conflicts of interest.