Preoperative Concurrent Chemotherapy and Intensity Modulated Radiotherapy (IMRT) in Locally Advanced Rectal Cancer

Inclusion Criteria:

• Pathologically proven diagnosis of adenocarcinoma of the rectum
• Clinically determined to be stage T3 or T4,N0-N2, and M0 -staged by MRI or transrectal ultrasound of the rectum
• Patients who are medically operable and who have resectable adenocarcinoma of the rectum at least <15cm from the anal verge
• Adequate liver/renal and haematological function.
• Eastern Cooperative Oncology Group (ECOG) performance 0-2
• Age ≥ 18 years

• Full blood count obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:

  • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Haemoglobin ≥ 8.0 g/dl
• Serum creatinine within normal institutional limits or creatinine clearance ≥ 50 ml/min
• Bilirubin within normal institutional limits
• AST and ALT < 2.5 x the IULN
• Patient must sign study specific informed consent prior to study entry

Exclusion Criteria:

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Prior systemic chemotherapy for colorectal cancer; note that prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Severe, active comorbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months
  • Transmural myocardial infarction within the last 6 months
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol.
  • Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
  • Known, existing uncontrolled coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks.
  • Major surgery within 28 days of study enrollment (other than diverting colostomy)
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
• Prior allergic reaction to capecitabine
• Any evidence of distant metastases (M1)
• A synchronous primary colon carcinoma
• Extension of malignant disease into the anal canal
• Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn's disease that results in
• malabsorption; significant bowel resection that would make one concerned about the absorption of capecitabine) or malabsorption syndrome that would preclude feasibility of oral chemotherapy (capecitabine)
• Participation in any investigational drug study within 28 days of study enrollment