608P - Excite: a phase II trial of preoperative cetuximab, irinotecan and capecitabine plus radiotherapy (RT) in MRI-defined locally advanced rectal cancer...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Cytotoxic agents
Surgical oncology
Colon and Rectal Cancer
Biological therapy
Radiation oncology
Presenter Simon Gollins
Authors S. Gollins1, A.S. Myint2, M. Saunders3, S. Susnerwala4, D. Sebag-Montefiori5, S. Beare6, E. Williams6, N. West7, M. Jitlal6
  • 1North Wales Cancer Treatment Centre, LL18 5UJ - Rhyl/UK
  • 2Clinical Oncology, Clatterbridge Cancer Centre, Liverpool/UK
  • 3Clinical Oncology, The Christie Hospital NHS Foundation Trust, Manchester/UK
  • 4Clinical Oncology, Royal Preston Hospital, Preston/UK
  • 5Oncology, University of Leeds, Leeds/UK
  • 6Cr Uk & Ucl Cancer Trials Centre, University College London, W1T 4TJ - London/UK
  • 7Pathology & Tumour Biology, University of Leeds, Leeds/UK



This phase II trial examined combining cetuximab, irinotecan and capecitabine concurrently with RT in the preoperative downstaging of LARC.


Patients (pts) had rectal adenocarcinoma with locally advanced/borderline unresectable disease on MRI. KRAS/BRAF was not assessed before treatment. Pts had pelvic RT to 45 Gy in 25 daily fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m2 twice daily 5 days/week. They also received intravenous (IV) cetuximab at 400 mg/m2 one week before RT then weekly at 250 mg/m2 weeks 1-5 of RT plus IV irinotecan weekly at 60 mg/m2 weeks 1-4 of RT. Surgical resection was stipulated at 8 weeks after chemoradiation (CRT) with primary end point histological circumferential resection margin (CRM) negative rate.


From Apr 2009-Oct 2011 82 pts were recruited. At baseline: male/female 61/21, median age 62, WHO PS 0/1/missing 60/19/3. On MRI tumour was T2/3/4 in 6/67/9 and N0/1/2 in 14/41/27 pts, mesorectal fascia or levator-sphincter complex was threatened (≤ 1mm gap) in 45 (55%), definitely involved in 21 (26%) and breached in 16 pts (20%). 2 pts did not commence RT and were withdrawn from trial treatment. The no. (%) of significant acute toxicities were diarrhoea grade (Gr)3 20 (25%), acneiform rash Gr3 7 (9%), fatigue Gr3 6 (8%), thrombotic event Gr3 1 (1%) and Gr4 5 (6%) and febrile neutropenia Gr3 1 (1%) and Gr4 1 (1%). 75 pts had surgery (36 anterior resection, 37 abdominoperineal, 2 Hartmans). Post-resection histology showed a negative CRM (>1mm) in 67 (89%), a pathological complete response (pCR) (T0N0) in 14 (19%), T0/1/2/3/4 in 15/2/16/40/2 and N0/1/2 in 51/15/9 pts. 38 of the 75 resected pts (51%) had their T and 49 of 63 (78%) their N1-2 stage downstaged. 5 pts with a clinical CR (cCR) post CRT did not have surgery and were alive with no evidence of disease at 8, 12, 14, 24 and 26 m.


EXCITE is the largest reported phase II trial of a triplet CRT regime including EGFR targeted therapy in LARC, showing acceptable toxicity and compliance. In MRI-defined locally advanced/borderline unresectable disease a combined pCR + cCR rate of 19/80 (24%) is promising. Data on KRAS and BRAF influence will be available by Aug 2012.


S. Gollins: Research funding grants from Merck and Pfizer Honoraria from Roche (Advisory Boards).

All other authors have declared no conflicts of interest.