Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer using an oxaliplatin-containing regimen: a phase II study

ABSTRACT

The combination of radiation. 5-fluorouracil and oxallplatin 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 four-field technique to a dose of 50.4 Gy 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 130 mg/m[2] on day 1 plus 30 minute infusion of 100 mg/m[2] L-folinic acid and continuous infusion of fluorouracil. 350 mg/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 [6 7.4%]. 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 down staging was diagnosed in 70.5% [31 out of 44 patients]. 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 down staging and sphincter saving surgery are encouraging. Further phase III studies are needed for better evaluation of the value of such regimen