Table 1 Inclusion and exclusion criteria

General

Age ≥ 18 years

ECOG performance score ≤ 1

Written informed consent

Staging done within 5 weeks prior to randomization

Adequate potential for follow-up

Mentally and physically fit for chemotherapy

Adequate blood counts:

White blood cell count ≥4.0 x 10⁹/L

Platelet count ≥100 x 10⁹/L

Clinically acceptable haemoglobin levels

Creatinine levels indicating renal clearance ≥ 50 ml/min

Bilirubin < 35 μmol/L

Primary tumour characteristics

Biopsy proven rectal adenocarcinoma*

Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI:

cT4a

cT4b

cN2

Extramural vascular invasion (EMVI+)

Involved mesorectal fascia (MRF+)

Metastatic lateral lymphnodes (LN+)

Exclusion criteria

Extensive tumour growth into sacrum above S3

Tumour involving lumbosacral nerve roots

Distant metastasis (M1)

Recurrent rectal cancer

FAP or HNPCC

Active Crohn’s disease or ulcerative colitis

Concomitant malignancies (except basocellular carcinoma or in-situ cervical carcinoma)

Known DPD deficiency

Contraindications to MRI (e.g. pacemaker)

Inability to give informed consent

Concurrent uncontrolled medical condition

Any investigational treatment for rectal cancer within past month

Pregnancy or breast feeding

Known malabsorption syndromes or lack of physical integrity of upper gastrointestinal tract

Myocardial infarction within past 12 months or clinically significant cardiac disease

Symptoms or history of peripheral neuropathy