ABSTRACT
The combination of radiation, 5-fluorouracil and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in phase 1 trials. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting. Between December 2003 and Jan 2006, 46 patients with locally advanced rectal adenocarcinoma entered the study. Radiotherapy was delivered with a fourfield technique to a dose of 50.4Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5 [from days 1-5 and 29-33] in the form of oxalipatin 130mg/m[2] on day 1 plus 30 minute infusion of 100mg/m[2] L-folinic acid and continuous infusion of fluorouracil 350mg/m[2] for 5 days. Surgery was planned 6 weeks later. All patient completed treatment without modification except 10/46 patients [21.7%] who experienced grade 3/4 toxicity which necessitates treatment interruption and further dose reduction. Surgery was performed in 44 patients as 2 cases developed metastasis before the time of the planned surgery. An objective response was seen in 31 patients [67.4%]. Sphincter-saving surgery was possible in 27 patients [61.4%]. No postoperative deaths occurred. In 5/44 patients [11.4%] the operative specimen was sterilized and in 2/44 patients [4.5%] only very few residual malignant cells difficult to find microscopically were detected. Pathological downstaging was diagnosed in 70.5% [31 out of 44 patient]. Local and distant progression occurred later in 9 patients and the 2-year event-free and overall survival were 83% and 91% at a median follow up time of 20 months. The median event-free and overall survival durations were 12 and 22.5 months respectively. The event-free duration ranged from 5 to 34 months while the overall survival duration ranged from 13 to 36 months. Such a combined preoperative chemoradiotherapy using an oxaliplatin-containing regimen is well tolerated with no increase in surgical morbidity. The rates of pathological downstaging and sphincter-saving surgery are encouraging. Further phase III studies are needed for better evaluation of the value of such regimen