Further inclusion criteria were an Eastern Cooperative Oncology Group performance status 0�C2 and adequate haematological (neutrophils 1.5 �� 109l?1 and platelets 100 �� 109l?1), renal (calculated creatinine clearance >50mlmin?1) and liver function (serum bilirubin 1.5 upper limit of normal range, liver transaminase or alkaline phosphatase selleck catalog concentrations 2.5 upper limit of normal range). No upper age limit was defined. Exclusion criteria were metastatic disease, previous chemotherapy for colorectal cancer or prior radiotherapy to the pelvis, history of another malignancy within the last 5 years, any contraindication to radiotherapy, clinically significant cardiac disease, malabsorption syndrome, peripheral neuropathy grade 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC version 3.

0), serious uncontrolled infection, concomitant treatment with any nucleoside analogue, known dihydropyrimidine dehydrogenase deficiency and psychiatric disorders or conditions interfering with compliance for oral drug intake. Pregnant or lactating woman were excluded. All patients provided written informed consent. The study protocol was approved by a local independent ethics committee and conducted in accordance with the Declaration of Helsinki. Pretreatment evaluation Before study entry, all patients were assessed by a multidisciplinary team comprising medical, radiation and surgical oncologists, gastroenterologists and radiologists. Patients underwent a medical history, physical examination, biopsy, ECG and staging studies (chest X-ray, abdominal�Cpelvis computed tomography scan, colonoscopy and endorectal ultrasound).

Pelvic MRI was optional but recommended for all patients with low-lying or T4 tumours. Complete laboratory tests included a full blood count, electrolytes, creatinine, liver transaminases, alkaline phosphatase, total bilirubin and carcinoembryonic antigen measurement. Treatment Radiotherapy Megavoltage equipment was used with 6�C18MV. Radiotherapy was delivered through three to four portal fields to the tumour and lymphonodal regions, and perirectal soft tissue structures at risk of microscopic disease. All patients received 45Gy, with a daily fraction of 1.8Gy given 5 days per week for 5 consecutive weeks. If treatment was interrupted, the dose was increased by 1�C2 fractions.

Chemotherapy Treatment consisted of a single cycle of XELOX (oral capecitabine 1000mgm?2 twice daily on days 1�C14 plus a 2-h intravenous infusion of oxaliplatin 130mgm?2 on day 1), followed by CAPOX combined with RT (capecitabine 825mgm?2 twice daily on days 22�C35 and 43�C56, and oxaliplatin 50mgm?2 on days 22, 29, 43 and 50; Figure 1). Chemotherapy and radiotherapy were interrupted if grade 3 or 4 toxicity was encountered (except for anaemia). Study Batimastat treatment was restarted when toxicity had resolved to grade 1. Dose reductions were required after grade 3�C4 toxicity.