Short- and long-term outcomes of neoadjuvant-synchronus S-1+radiotherapy for locally advanced rectal cancer: Multicenter phase II study.

720 Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug S-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with S-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) was administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision was performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT, short-term clinical outcomes, rate of curative resection, and pathological response (grade2/3). Results: This trial included 37 patients (clinical StageIIA: 8, IIIB: 19, IIIC: 10; tumor located in the upper rectum; 4, the lower rectum; 33). A complete treatment of neoadjuvant CRT was found in 86.5% of patients (95%CI;75.5-97.5%), and an adverse event (grade 3/4) occurred in 4 patients(11.1%). Response rate (PR/CR;RECIST 1.0) was 56.8% (95%CI; 40.8-72.7%), and pathologic response rate (grade2/3) was 48.6% (95%CI; 32.5-64.8%). The median operating time was 448.5 min (IQR 340.5-505.5), and median blood loss was 422.5 mL (IQR 182.5-1125). Grade 3-4 postoperative complications occurred in 6 (16.7%) patients. The most common grade 3 or 4 postoperative complication was anastomotic leakage (2 [5.6%]). The 3-year overall survival rate was 88.5%. The 3-year disease free survival rate was 70.9%. Median length of follow-up was 42 months. Conclusions: A neoadjuvant-synchronus S-1+Radiotherapy for locally advanced rectal cancer is feasible in terms of pathological response, adverse events, accompany with favorable long-term outcome. Clinical trial information: 03396.

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The significance and long-term clinical outcome of preoperative chemoradiotherapy using S-1 plus Irinotecan for locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.819 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 819-819

Author(s):

Kei Kimura ◽

Naohito Beppu ◽

Kiyoshi Tsukamoto ◽

Tomoki Yamano ◽

Masafumi Noda ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Rate ◽

Radical Surgery ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Free Survival ◽

Grade 3

819 Background: Preoperative chemoradiotherapy regimen using S-1 plus Irinotecan is still under clinical investigation. The aim of this study was to investigate the significance and the long-term outcomes of this regimen for locally advanced rectal cancer. Methods: Between 2009 and 2016, 81 patients underwent radical surgery after preoperative chemoradiotherapy. Radiotherapy was administered in total 45Gy with 1.8Gy/day for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m2 on days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan was infused with dose of 80 mg/m2 on days 1, 8, 22, and 29. 6-9 weeks after the completion of the treatment, radical surgery was performed. The median follow-up was 35.3 months. Results: Of the 81 patients, 76 (93.8%) completed treatment of chemoradiotherapy. Relative dose intensity of CPT-11 was 92.8%, S-1 was 90.1%. 79 (97.5%) patients completed the radiotherapy. 18 patients (22.2%) had ≧Grade 3 hematologic toxicity (leukopenia; 15 patients, neutropenia; 16 patients ). 23 patients (28.3%) had ≧Grade 3 nonhematologic toxicity (diarrhea). In terms of the surgical procedure, 73 of 81 patients (90.1%) underwent sphincter-preserving surgery including 42 patients intersphincteric resection, and 8 patients (9.9%) underwent abdominoperineal resection. The tumor regression grade of 1/2/3(pCR) was 30/39/12(14.8%). In terms of long-term survival, 3-year local relapse-free survival rate was 96.7%, the recurrence-free survival rate was 71.6% and 3-year overall survival rate was 94.9%. Conclusions: Preoperative chemoradiotherapy using combined with Irinotecan as secondary drugs may result safe and feasible and accomplished favorable downstaging. This regimen was considered to be effective in patients with locally advanced rectal cancer.

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The comparison of mFOLFOXIRI with CAOX/SOX as neoadjuvant chemotherapy for locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.51 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 51-51

Author(s):

Tetsuji Terazawa ◽

Hiroyuki Kodama ◽

Hiroki Yukami ◽

Masahiko Aoki ◽

Takahiro Miyamoto ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Rate ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Distant Recurrence ◽

Locally Advanced Rectal Cancer ◽

Pathological Response ◽

R0 Resection ◽

Hand Foot Syndrome

51 Background: The standard therapy for the locally advanced rectal cancer (LARC) (Ra or Rb, T2Npsitive, T3/4Nany) is chemoradiotherapy (CRT) followed by surgery. The CRT prevents local recurrence, although problems such as complications or the improvement of distant recurrence still remain. Several studies about the neoadjuvant chemotherapy (NAC) without radiation showed favorable R0 resection rate and outcome, however the best regimen of NAC is unclear. The aim of this study is to investigate the efficacy and safety of mFOLFOXIRI and CAPOX/SOX as NAC. Methods: We examined the patients (pts) with LARC who were planned to receive mFOLFOXIRI (5FU 2400mg/m2/day1-2, leucovorin 200mg/m2, oxaliplatin 85mg/m2, irinotecan 150mg/m2, every 2 weeks) or CAPOX/SOX(capecitabine 2000mg/m2 or S-1 mg/m2 80day1-14, oxaliplatin 130mg/m2, day1, every 3weeks) for 8-12 weeks as NAC, retrospectively. Results: Forty-nine pts received mFOLFOXIRI and thirty-two pts received XELOX/SOX between Jan 2015 and Mar 2019. The characteristics of mFOLFOXIRI and XELOX/SOX were as follows; median age, 64 (37-80) and 65 (33-68); PS 0/1, 46(94%)/3(6%) and 14(44%)/18(56%); Ra/Rb-P, 4(8%)/45(92%) and 0/32; clinical T2/3/4, 4(7%)/27(55%)/19(39%) and 1(3%)/18(56%)/13(41%); clinical N0/1/2, 13(27%)/26(53%)/10(20%) and 7(22%)/17(53%)/8(25%). The pathological response rate which was defined as tumor affected area over one-third were 61.2% in mFOLFOXIRI and 65.6% in CAPOX/SOX including complete remission of 4.1% and 12.5%, respectively. Six of 49 pts withdrew from mFOLFOXIRI due to toxicities, whereas one of 32 pts from CAPOX/SOX. One pt received CRT after SOX because of lack of efficacy. The major grade 3/4 toxicities of mFOLFOXIRI were neutropenia (n = 22, 45%), thrombocytopenia and febrile neutropenia (n = 4, 8%) and anorexia (n = 3, 6%), whereas CAPOX/SOX neutropenia (n = 3. 9%), thrombocytopenia (n = 1, 3%) and hand-foot syndrome (n = 1, 3%). The one year of relapse free survival rate were 85.4% and 83.6%. Conclusions: Although the pathological response of mFOLFOXIRI was comparable with CAPOX/SOX, CAPOX/SOX was less toxic.The further investigation including 5 year overall survival rate rate was needed.

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