a randomised trial of preoperative radiotherapy for stage t3 adenocarcinoma of rectum

Conditions: Adenocarcinoma of Rectum

Summary: this is a multi-centre randomised trial comparing long course (lc) preoperative chemoradiation with short course (sc) preoperative radiotherapy for patients with localised t3 rectal cancer.

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.

Eligibility criteria:
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.

Keywords: rectal cancer radiotherapy chemotherapy chemoradiation adjuvant therapy