Should Oxaliplatin Be Added to Preoperative Chemoradiation?

Abstract

Oxaliplatin radiosensitizes human colon carcinoma cells in preclinical models and improves the efficacy of fluorouracil both in the palliative treatment of metastatic colorectal cancer and as adjuvant treatment after complete resection of intraperitoneal colon cancer. Its combination with FU and radiation in the preoperative treatment of rectal cancer may thus improve both the control of micrometastases at distant sites and local tumor shrinkage before surgery. High rates of tumor sterilization at surgery were indeed observed in multiple phase I–II studies, testing the combination of oxaliplatin with fluorouracil and preoperative radiation, particularly when a weekly schedule was used for oxaliplatin administration. Five randomized trials have then been launched to investigate the addition of weekly oxaliplatin to preoperative radiation and concomitant fluorouracil or capecitabine. Safety and activity data have now been reported for four of these studies indicating that adding oxaliplatin to a fluoropyrimidine does not improve primary tumor response (with rates of pathological complete responses identical or nearly identical to the control arms in two studies and only 4–5% higher in the other two and other measures of response to neoadjuvant chemoradiation similarly distributed between the groups treated with or without oxaliplatin) but is associated with significantly increased toxicity. Although further follow-up is required to assess the impact of adding oxaliplatin on long-term outcomes, these results indicate that, at the moment, oxaliplatin should not be added to preoperative chemoradiation. Alternative strategies are thus to be developed to improve primary tumor response in locally advanced rectal cancer.