A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

Objective:

• The objective is, in patients with T3 clinically resectable carcinoma of the rectum, to demonstrate that the local recurrence rate in patients treated with a long course (LC) of pre-operative radiotherapy with continuous infusion 5-FU is lower than that in patients treated with a short course (SC) of pre-operative radiotherapy with early surgery

Eligibility Criteria:

• The main eligibility criteria are that the patient has clinically resectable adenocarcinoma of the rectum, a clinical stage T3 tumour whose lower border is within 12 cm of the anal verge, and no evidence of distant metastases.

Endpoints:

• Primary endpoint is local recurrence.
• Secondary endpoints are overall survival, toxicity, abdminoperineal resection rate, quality of life.

Treatment arms:

• SC arm: Radiotherapy (RT) 25 Gy in 5 fr in 1 week to be followed by surgery within 1 week and 6 cycles of postoperative chemotherapy 5FU/Folinic acid.
• LC arm: RT 50.4 Gy in 28 fr in 5½weeks with 5FU 225 mg/m2/day throughout the course of RT, to be followed by surgery 4-6 weeks after completion of RT. 4 cycles of adjuvant 5FU/Folinic acid will be given.

Inclusion criteria

All of the following must apply:

• Pathologically documented and clinically resectable adenocarcinoma of the rectum.
• The patient must be considered by the surgeon to be suitable for a curative resection.
• The patient must be considered by the radiation oncologist to have no contraindication to pre-operative radiotherapy.
• Clinical T3 stage tumour on endorectal ultrasound or MRI. When endorectal ultrasound cannot be performed satisfactorily due to a technical reason, such as stenosis or proximity of the tumour, and MRI is not available, infiltration of perirectal fat on CT scan is also acceptable.
• Tumour with lower border within 12 cm from anal verge on rigid sigmoidoscopy.
• ECOG performance status 0, 1 or 2.
• Adequate bone marrow function with neutrophil count at least 1.5 x 109/L and platelet count at least 100 x 109/L.
• Adequate liver function with bilirubin and alanine aminotransferase (ALT) <= 1.5 times the upper limit of normal.
• Adequate renal function with serum creatinine <= 1.5 times the upper limit of normal.
• Accessibility for treatment and follow-up.
• Written informed consent.

Exclusion criteria

• None of the following must apply:
• Evidence of distant metastases.
• Recurrent rectal cancer.
• Unstable cardiac disease or clinically significant active infection.
• Other cancer in the last 5 years except treated non-melanoma skin cancer or carcinoma in situ of the cervix.
• Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures.
• Contraindication to insertion of a suitable indwelling venous catheter e.g. implantable central venous device (infuse-a-port), Hickman catheter or peripherally inserted central catheter.
• Prior pelvic or abdominal radiotherapy.