Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum.
BACKGROUND
In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection.


METHODS
This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4-12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy.


CONCLUSIONS
In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial.


BACKGROUND
Clinical trial identifier BACCHUS: NCT01650428.
Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK. rob.glynnejones@nhs.net.
R
R
Glynne-Jones
Cancer Research UK & University College London Cancer Trials Centre, London, UK.
N
N
Hava
Division of Imaging Sciences & Biomedical Engineering, Kings College London, London, Department of Radiology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, SE1 7EH, UK.
V
V
Goh
Pharmacy, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK.
S
S
Bosompem
University College, London Cancer Institute, 72 Huntley St., London, WC1E 6AA, UK.
J
J
Bridgewater
Department of Medical Oncology, Royal Marsden Hospital, London & Surrey, UK.
I
I
Chau
Radiotherapy Department, Guys and St Thomas's Hospital, Westminster Bridge Road, London, SE1 7EH, UK.
A
A
Gaya
Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
H
H
Wasan
Department of Surgery, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire, UK.
B
B
Moran
Radiotherapy Department, Beatson Oncology Centre, 1053 Great Western Rd, Glasgow G12 0YN, UK.
L
L
Melcher
Radiotherapy Department, North Middlesex Hospital, Sterling Way, London N18 1QX, UK.
A
A
MacDonald
Radiotherapy Department, Royal Devon & Exeter Hospital, Barrack Rd, Exeter, Devon EX2 5DW, UK.
M
M
Osborne
Cancer Research UK & University College London Cancer Trials Centre, London, UK.
S
S
Beare
Cancer Research UK & University College London Cancer Trials Centre, London, UK.
M
M
Jitlal
Cancer Research UK & University College London Cancer Trials Centre, London, UK.
A
A
Lopes
Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK.
M
M
Hall
Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, United Kingdom.
N
N
West
Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, United Kingdom.
P
P
Quirke
Department of Radiology, Paul Strickland Scanner Centre, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK.
Wai-Lup
WL
Wong
Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK.
M
M
Harrison
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D013505:Digestive System Surgical Procedures; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab