Synchronous postoperative adjuvant chemoradiation therapy for locally advanced carcinoma of the rectum

The adjuvant management of locally advanced rectal cancer has been the subject of much debate over the past 10 years. Whilst it is now widely accepted that combined chemoradiation therapy is the treatment of choice for adjuvant therapy following resection of high-risk tumours, there is still no clear answer on the sequencing of the two modalities in the postoperative setting.

Soon after the NCI in the United States issued its recommendations on the management of resected rectal cancer, we decided to commence a phase 2 study to collect data prospectively on the toxicity of postoperative combined chemoradiation therapy. Radiation therapy was given early in combination with bolus chemotherapy using 5-fluorouracil ( n=80). The prescribed radiation dose was 50.4 Gy in 28 fractions, and the chemotherapy was 450 mg/m(2) given with fractions 1 - 3 and 26 - 28. On completion of the radiation therapy the patient was given a further four cycles of bolus 5-fluorouracil at monthly intervals. The patients were then closely monitored for side effects from the therapy and for signs of local and distant relapse.

Acute toxicity of the therapy was significant, with 16% of patients experiencing severe bowel morbidity. The other major side effects of the therapy were skin reactions, neutropenia and bladder problems. Late bowel toxicity was also severe. The local in field relapse rate was 10%. The majority of relapses were at distant sites, mostly in the liver and lungs. The actuarial survival at 5 years was 55%.

We conclude that the combined adjuvant postoperative chemoradiation therapy using this protocol is effective but has significant acute and late morbidity. The optimum regimen for those patients requiring postoperative adjuvant therapy is yet to be determined.