Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Surgery Today
Published in: Surgery Today 1/2018

01-01-2018 | Original Article

Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG)

Authors: Yasuhiro Miyake, Junichi Nishimura, Takeshi Kato, Masataka Ikeda, Masaki Tsujie, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Mitsugu Sekimoto, Riichiro Nezu, Yuichiro Doki, Masaki Mori, Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO)

Published in: Surgery Today | Issue 1/2018

Login to get access

Abstract

Purpose

Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection.

Methods

The primary endpoint was the 3-year disease-free survival (DFS). A randomized non-inferiority study compared UFT/LV to UFT/PSK. The overall survival, adverse events, compliance, and quality of life were also investigated as the secondary endpoints.

Results

Between March 2006 and December 2010, 357 patients were randomized to UFT/PSK (n = 178) or UFT/LV (n = 179) (median age 65 years, colon/rectum 67.4/32.6%, stage IIB/IIIA/IIIB/IIIC 11.1/15.7/55.0/18.2%). The 3-year DFS rate was 82.3% in those receiving UFT/LV and 72.1% in those receiving UFT/PSK. The non-inferiority of UFT/PSK adjuvant therapy to UFT/LV therapy was not verified (−9.06%, 90% confidence interval −17.06 to −1.06%). The 3-year overall survival rate was 95.4% in those receiving UFT/LV and 90.7% in those receiving UFT/PSK.

Conclusions

As adjuvant chemotherapy for stage IIB and III colorectal cancer patients, UFT/PSK adjuvant therapy was not non-inferior to UFT/LV therapy with respect to the DFS.
Literature
1.
Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322(6):352–8.CrossRefPubMed
2.
Colvin H, Mizushima T, Eguchi H, Takiguchi S, Doki Y, Mori M. Gastroenterological surgery in Japan: the past, the present and the future. Ann Gastroenterol Surg. 2017;1:5–10.CrossRef
3.
Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y, et al. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011;67(3):587–96.CrossRefPubMed
4.
Sakamoto J, Hamada C, Yoshida S, Kodaira S, Yasutomi M, Kato T, et al. An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer. Br J Cancer. 2007;96(8):1170–7.CrossRefPubMedPubMedCentral
5.
Lembersky BC, Wieand HS, Petrelli NJ, O’Connell MJ, Colangelo LH, Smith RE, et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006;24(13):2059–64.CrossRefPubMed
6.
Shimada Y, Hamaguchi T, Mizusawa J, Saito N, Kanemitsu Y, Takiguchi N, et al. Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205. Eur J Cancer. 2014;50(13):2231–40.CrossRefPubMed
7.
Ward SE, Kaltenthaler E, Cowan J, Marples M, Orr B, Seymour MT. The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer. Br J Cancer. 2006;95(1):27–34.CrossRefPubMedPubMedCentral
8.
Fisher M, Yang LX. Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res. 2002;22(3):1737–54.PubMed
9.
Lu H, Yang Y, Gad E, Wenner CA, Chang A, Larson ER, et al. Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clin Cancer Res. 2011;17(1):67–76.CrossRefPubMed
10.
Ono Y, Hayashida T, Konagai A, Okazaki H, Miyao K, Kawachi S, et al. Direct inhibition of the transforming growth factor-beta pathway by protein-bound polysaccharide through inactivation of Smad2 signaling. Cancer Sci. 2012;103(2):317–24.CrossRefPubMed
11.
Hirahara N, Fujioka M, Edamatsu T, Fujieda A, Sekine F, Wada T, et al. Protein-bound polysaccharide-K (PSK) induces apoptosis and inhibits proliferation of promyelomonocytic leukemia HL-60 cells. Anticancer Res. 2011;31(9):2733–8.PubMed
12.
Jimenez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, et al. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis. BMC Cancer. 2008;8:78.CrossRefPubMedPubMedCentral
13.
Ito K, Nakazato H, Koike A, Takagi H, Saji S, Baba S, et al. Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up. Int J Colorectal Dis. 2004;19(2):157–64.CrossRefPubMed
14.
Maehara Y, Moriguchi S, Sakaguchi Y, Emi Y, Kohnoe S, Tsujitani S, et al. Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. J Surg Oncol. 1990;45(3):169–72.CrossRefPubMed
15.
Niimoto M, Hattori T, Tamada R, Sugimachi K, Inokuchi K, Ogawa N. Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for 5 years. Jpn J Surg. 1988;18(6):681–6.CrossRefPubMed
16.
Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, et al. Adjuvant immunochemotherapy with oral tegafur/uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer. 2004;90(5):1003–10.CrossRefPubMedPubMedCentral
17.
Torisu M, Hayashi Y, Ishimitsu T, Fujimura T, Iwasaki K, Katano M, et al. Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol Immunother. 1990;31(5):261–8.CrossRefPubMed
18.
Ohwada S, Kawate S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, et al. Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial. Dis Colon Rectum. 2003;46(8):1060–8.CrossRefPubMed
19.
Sadahiro S, Suzuki T, Maeda Y, Tanaka A, Kamijo A, Murayama C, et al. Effects of preoperative immunochemoradiotherapy and chemoradiotherapy on immune responses in patients with rectal adenocarcinoma. Anticancer Res. 2010;30(3):993–9.PubMed
20.
Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990;9(12):1447–54.CrossRefPubMed
21.
Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343–51.CrossRefPubMed
22.
Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465–71.CrossRefPubMed
23.
Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198–204.CrossRefPubMed
24.
Mieno H, Yamashita K, Hosoda K, Moriya H, Higuchi K, Azuma M, et al. Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer. Surg Today. 2017. doi:10.​1007/​s00595-017-1512-z.PubMed
25.
26.
Honma Y, Yamada Y, Terazawa T, Takashima A, Iwasa S, Kato K, et al. Feasibility of neoadjuvant S-1 and oxaliplatin followed by surgery for resectable advanced gastric adenocarcinoma. Surg Today. 2016;46(9):1076–82.CrossRefPubMed
27.
Beppu N, Yoshie H, Kimura F, Aihara T, Doi H, Kamikonya N, et al. The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer. Surg Today. 2016;46(10):1123–31.CrossRefPubMed
28.
Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 2012;17(1):1–29.CrossRefPubMed
29.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.CrossRefPubMedPubMedCentral
30.
Ooshiro M, Sugishita YI, Tanaka H, Koide K, Nagashima M, Katoh R. Regulation of perioperative immunological changes following laparotomy: effects of biological response modifier (BRM) on surgical stress. Immunol Lett. 2004;93(1):33–8.CrossRefPubMed
31.
Okuzawa M, Shinohara H, Kobayashi T, Iwamoto M, Toyoda M, Tanigawa N. PSK, a protein-bound polysaccharide, overcomes defective maturation of dendritic cells exposed to tumor-derived factors in vitro. Int J Oncol. 2002;20(6):1189–95.PubMed
Metadata
Title
Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG)
Authors
Yasuhiro Miyake
Junichi Nishimura
Takeshi Kato
Masataka Ikeda
Masaki Tsujie
Taishi Hata
Ichiro Takemasa
Tsunekazu Mizushima
Hirofumi Yamamoto
Mitsugu Sekimoto
Riichiro Nezu
Yuichiro Doki
Masaki Mori
Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO)
Publication date
01-01-2018
Publisher
Springer Japan
Published in
Surgery Today / Issue 1/2018
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-017-1555-1

Other articles of this Issue 1/2018

Surgery Today 1/2018 Go to the issue

Original Article

Frey’s procedure for chronic pancreatitis improves the nutritional status of these patients

Original Article

The efficacy of active drainage for preventing postoperative organ/space surgical site infections in patients with Crohn’s disease

Acknowledgment

Acknowledgment to reviewers

Original Article

Short- and long-term outcomes of the Frey procedure for chronic pancreatitis: a single-center experience and summary of outcomes in Japan

Original Article

Analysis of gender-based differences among surgeons in Japan: results of a survey conducted by the Japan Surgical Society. Part 1: Working style

Original Article

Sentinel node biopsy for axillary management after neoadjuvant therapy for breast cancer: a single-center retrospective analysis with long follow-up