Induction Chemotherapy Before or After Preoperative Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer

Inclusion Criteria: * Male and female patients with histologically confirmed diagnosis of rectal cancer localised 0 - 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum) * Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure. * MRI-defined inclusion criteria: presence of at least one of the following high risk conditions: any cT3 (clinical stage tumor-3) if the distal extent of the tumor is \< 6 cm from anocutaneous line or cT3 in the middle third of the rectum (≥ 6-12 cm) with MRI evidence of extramural tumor spread into the mesorectal fat of more than 5 mm (\>cT3b), or resectable cT4 tumors, or any clear cN+ (clinical staging nodes) based on MRI-criteria * Trans-rectal endoscopic ultrasound (EUS) is additionally used when MRI is not definitive to exclude early cT1/T2 disease in the lower third of the rectum or early cT3a/b tumors in the middle third of the rectum. * Spiral-CT of the abdomen and chest to exclude distant metastases. * Aged at least 18 years. No upper age limit. * WHO/ECOG (World Health Organisation/Eastern Cooperative Oncology Group) Performance Status ≤ 1 * Adequate haematological, hepatic, renal and metabolic function parameters: Leukocytes ≥ 3.000/mm\^3, absolute neutrophil count (ANC) ≥ 1.500/mm\^3, platelets ≥100.000/mm\^3, Hb \> 9 g/dl; Serum creatinine ≤ 1.5 x upper limit of normal; Bilirubin ≤ 2.0 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase (AP) ≤ 3 x upper limit of normal * Informed consent of the patient Exclusion Criteria: * Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy * Distant metastases (to be excluded by CT scan of the thorax and abdomen) * Prior antineoplastic therapy for rectal cancer * Prior radiotherapy of the pelvic region * Major surgery within the last 4 weeks prior to inclusion * Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. * Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly). * On-treatment participation in a clinical study in the period 30 days prior to inclusion * Previous or current drug abuse * Concomitant other antineoplastic therapy * Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder * Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment * Chronic diarrhea (\> grade 1 according NCI CTCAE) * Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO (International Federation of Gynecology and Obstetrics) stage 0-1), if the patient is continuously disease-free * Known allergic reactions on study medication * Known dihydropyrimidine dehydrogenase deficiency * Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial)