A prospective feasibility study to evaluate neoadjuvant-synchronous S-1 with radiotherapy for locally advanced rectal cancer: A multicentre phase II trial

Abstract

Treatment results of locally advanced rectal cancer without preoperative chemoradiotherapy (CRT) in Japan do not differ from those of Western countries. Preoperative CRT with new anticancer agents may decrease local recurrence rate and prevent distant metastases, thus improving survival. We conducted a trial to evaluate feasibility of neoadjuvant CRT using S-1 in patients with locally advanced rectal cancer. A multi-institutional (17 specialized centres), interventional, phase II trial was conducted from April 2009 to August 2011. Patients fulfilling the following requirements before neoadjuvant CRT were included: histologically proven rectal carcinoma; tumour in the upper or lower rectum; cancer classified as T3-4 N0-3 M0. Neoadjuvant CRT with S-1 (80 mg/m/day on days 1-5, 8-12, 22-26, and 29-33) and irradiation (total 45 Gy/25 fr, 1.8 Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision with D3 lymphadenectomy was performed during weeks 4 and 8 after completion of neoadjuvant CRT. The primary endpoint was completion rate of neoadjuvant CRT. Secondary endpoints were response rate to neoadjuvant CRT, short-term clinical outcomes, curative resection rate, and pathologic response (grade 2/3). Of the 37 patients included, 86.5% completed neoadjuvant CRT (95% CI, 75.5-97.5%), and 10.8% (4) experienced an adverse event (grade 3/4). Response rate (RECIST 1.0) was 56.8% (95% CI, 40.8-72.7%), and pathologic response rate was 48.6% (95% CI, 32.5-64.8%). This study demonstrated that neoadjuvant-synchronous S-1+radiotherapy for locally advanced rectal cancer was feasible in terms of pathologic response and adverse events. Registration number: UMIN-CTR, No. C003396.

Long-term outcomes of neoadjuvant-synchronous S-1 plus radiotherapy for locally advanced rectal cancer: a multi-institutional prospective phase II study

“…Sato et al reported good outcomes, with increased rates of completing treatment (86.6%) and pathological complete response (pCR; 34.7%), in a phase II trial of neoadjuvant preoperative CRT with S-1 plus irinotecan and radiation in patients with locally advanced rectal cancer 9) . We also conducted a phase II trial to evaluate neoadjuvant-synchronous S-1 with radiotherapy for locally advanced rectal cancer and demonstrated its short-term safety 10) . There are only a few reports on the short-term outcomes of neoadjuvant CRT using S-1 for locally advanced rectal cancer, and long-term outcomes for patients receiving this regimen remain unknown.…”

An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis

“…From April, 2009 to August, 2011, a total of 37 patients diagnosed with primary rectal cancer were prospectively enrolled in a multicenter phase II study (UMIN ID 03396). The trial design and eligibility criteria have been previously reported (12). Of the 37 patients, 26 whose biopsy specimens were available for microarray analysis were investigated in the present study.…”

“…The details of the CRT were previously described (12). CRT was administered concurrently with four cycles of chemotherapy.…”

“…It was also reported that preoperative CRT using concurrent S-1 and irinotecan achieved excellent long-term survival with acceptable adverse events in patients with rectal cancer (11). We conducted a multi-institutional phase II trial to evaluate the feasibility of preoperative S-1 plus radiotherapy for rectal cancer (UMIN ID: 03396) (12). Our results demonstrated that the treatment completion rate was comparable with that reported by studies conducted in western countries; a high rate of R0 and a low rate of occurrence of adverse side effects were demonstrated (12).…”

Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study

“…The oral fluoropyrimidine S-1, an anti-cancer drug invented in Japan, is designed to improve 5-FU's antitumor activity while reducing gastrointestinal toxicity 22) . Gimeracil, a dehydropyrimidine dehydrogenase (DPD) inhibitor, is reported to have a radio sensitizing property when combined with S-1 23) , and there have been several reports of CRT using S-1 for rectal cancer mainly from Japan [24][25][26] .…”