Radiochemotherapy in rectal cancer: the role of oxaliplatin

Abstract

Radiation therapy is well established in the treatment of early and locally advanced rectal cancer, where it has been used in both the pre-operative and postoperative settings. Pre-operatively, radiation therapy has been shown in a series of studies culminating in the Dutch total mesorectal excision (TME) study to significantly reduce the rate of local recurrence at 2 years. However, the overall rate of survival was not improved in this study because radiotherapy failed to reduce the incidence of distant metastases. Chemotherapy, however, may reduce distant metastatic spread, as well as increasing the rate of R0 resectability and sphincter-saving surgery when used in combination with radiotherapy in the neoadjuvant setting. Oxaliplatin is a prime candidate for radiochemotherapy in rectal cancer because it frequently has large and rapid cytoreductive effects in colorectal malignancies and has been shown in vitro and preclinical models to be radiosensitizing. In an Italian phase I/II study, weekly oxaliplatin combined with standard infusional 5-FU and pre-operative radiotherapy has shown low toxicity and promising antitumour activity. These encouraging results are now being followed up in a more extensive trials programme. A randomized trial comparing this regimen with standard infusional FUra and radiotherapy (STAR, Studio nazonaleTerapia neoAdiuvante Retto [National Study on Neoadjuvant Treatment of Rectal cancer]) is being launched in Italy. A new phase II study, CORE (Capecitabine, Oxaliplatin, Radiotherapy and Excision), is now in development in Europe and will use a similar weekly treatment regimen with an oral fluropyrimidine in place of infusional FUra, and a number of further oxaliplatin-based radiochemotherapy studies in rectal cancer are planned or in progress. In summary, radiochemotherapy appears to have the potential to significantly improve clinical outcomes in rectal cancer, and oxaliplatin-based treatment is proving central to its ongoing development.