Neoadjuvant Chemotherapy followed by Pre-operative Chemoradiation and Consolidation Chemotherapy before Surgery in High Risk Rectal Cancer: Multicentric Phase II Study

Prior treatment

• Previous radiotherapy on the pelvis

Other illness

• Clinically significant (active) cardiovascular disease, eg. cerebrovascular events (≤6 months), myocardial infarction (≤6 months), unstable angina, congestive decompensation of grade II or higher according to New York Heart Association (NYHA), cardiac arrhythmia under therapy.
• Gastrointestinal disorders with malabsorption syndrome, inability to take drugs through oral administration

Other

• Presence of genotypes associated with complete DPD enzyme deficiency

• Medial-distal Rectal Adenocarcinoma (up to 12 cm from the anal margin) histologically documented, stage T3c-dN1-2M0, MRF+, T4N0-2MO (potentially resectable), EMVI -/+
• Absence of clinically significant cardiopathy
• Absence of pregnancy or ongoing breast-feeding
• Written informed consent
• Age > 18
• ECOG PS 0-1
• Measurable disease according to RECIST 1.1
• Able to comprehend risks and advantages of the study
• Neutrophils ≥ 1.5x10^3/μL; Platelets ≥ 100x10^3/μL; Total Bilirubin ≤ 1.5 (UNL); ALT and AST ≤ 2.5 UNL, Alkaline Phosphatase ≤ 2.5 UNL; Creatinine clearance >50 ml/min or Creatinine ≤ 1.5 UNL; Proteinuria (stick) <2+ (se ≥ 2+, perform a 24h urine collection and verify that the value is ≤1 g/24 hr).
• Absence of mutational state with complete deficit of dihydropyrimidine dehydrogenase (DPD) enzyme; presence of mutations associed with partial DPD deficit does not exclude patient eligibility (Fluoropyrimidine dose reduction is expected)
• Absence of neuropathy grade > 1 associated to concomitant illnesses
• Absence of other malignancies within the last 5 years, except for skin carcinoma and carcinoma in situ of the cervix.