Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR)

Chapter 1

Zero over n reports

abstract

Multicenter, Randomized, Phase Three Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR)

PURPOSE To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer.

MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage three to four and/or regional lymph node-positive rectal cancer were randomly assigned one to one to short-term radiotherapy (twenty-five Gy in five fractions over one week) followed by four cycles of chemotherapy (total neoadjuvant therapy) or chemoradiotherapy (fifty Gy in twenty-five fractions over five weeks, concurrently with capecitabine). Total mesorectal excision was undertaken six to eight weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin one hundred thirty mg per square meter, once a day on day one and capecitabine one thousand mg per square meter, twice a day from days one to fourteen) in the total neoadjuvant therapy group and six cycles of CAPOX in the chemoradiotherapy group. The primary end point was three-year disease-free survival.

RESULTS Between August twenty fifteen and August twenty eighteen, a total of five hundred ninety-nine patients were randomly assigned to receive total neoadjuvant therapy or chemoradiotherapy. At a median follow-up of thirty-five point zero months, three-year disease-free survival was sixty-four point five percent and sixty-two point three percent in total neoadjuvant therapy and chemoradiotherapy groups, respectively (hazard ratio, zero point eight eight three; one-sided ninety-five percent confidence interval, not applicable to one point one one; P is less than point zero zero one for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the total neoadjuvant therapy group had better three-year overall survival than the chemoradiotherapy group (eighty-six point five percent versus seventy-five point one percent; P equals point zero three three). Treatment effects on disease-free survival and overall survival were similar regardless of prognostic factors. The prevalence of acute grade three to five toxicities during preoperative treatment was twenty-six point five percent in the total neoadjuvant therapy group versus twelve point six percent in the chemoradiotherapy group (P is less than point zero zero one).

CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to chemoradiotherapy for locally advanced rectal cancer.