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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Rectal Cancer | Study Protocol

Preoperative chemoradiotherapy using tegafur/uracil, oral leucovorin, and irinotecan (TEGAFIRI) followed by oxaliplatin-based chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: the study protocol for a phase II trial

Authors: Shinya Abe, Kazushige Kawai, Hiroaki Nozawa, Kazuhito Sasaki, Koji Murono, Shigenobu Emoto, Yuichiro Yokoyama, Hiroyuki Matsuzaki, Yuzo Nagai, Yuichiro Yoshioka, Takahide Shinagawa, Hirofumi Sonoda, Yoko Yamamoto, Koji Oba, Soichiro Ishihara

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol.

Methods

Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery.

Discussion

Since previous findings showed a high percentage of grade 3–4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC.

Trial Registration

Japan Registry of Clinical Trials jRCTs031210660.
Appendix
Available only for authorised users
Literature
1.
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.CrossRefPubMed
2.
Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23.CrossRefPubMed
3.
de Campos-Lobato LF, Stocchi L, da Luz Moreira A, et al. Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol. 2011;18(6):1590–8.CrossRefPubMed
4.
Hofheinz RD, Wenz F, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13(6):579–88.CrossRefPubMed
5.
Hong YS, Nam BH, Kim KP, et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014;15(11):1245–53.CrossRefPubMed
6.
Glynne-Jones R, Counsell N, Quirke P, et al. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014;25(7):1356–62.CrossRefPubMed
7.
Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24(4):668–74.CrossRefPubMed
8.
Chua YJ, Barbachano Y, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010;11(3):241–8.CrossRefPubMed
9.
Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29–42.CrossRefPubMed
10.
Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702–15.CrossRefPubMed
11.
Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022;40(23):2546–56.CrossRefPubMed
12.
Marco MR, Zhou L, Patil S, et al. Consolidation mFOLFOX6 Chemotherapy after Chemoradiotherapy improves survival in patients with locally advanced rectal Cancer: final results of a Multicenter Phase II Trial. Dis Colon Rectum. 2018;61(10):1146–55.CrossRefPubMedPubMedCentral
13.
Kawai K, Sunami E, Hata K, et al. Phase I/II study of Preoperative Chemoradiotherapy with TEGAFIRI for locally advanced rectal Cancer. Clin Colorectal Cancer. 2018;17(3):240–6.CrossRefPubMed
14.
Amin MB, Edge SB, Greene FL, et al. AJCC cancer staging manual. Eighth edition ed. New York: Springer; 2017.CrossRef
15.
Rectum JSfCotCa. Japanese classification of Colorectal, Appendiceal, and Anal Carcinoma: the 3d English Edition [Secondary publication]. J Anus Rectum Colon. 2019;3(4):175–95.CrossRef
16.
Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the Colon and rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1–42.CrossRefPubMed
17.
Benson AB, Venook AP, Al-Hawary MM, et al. NCCN Guidelines Insights: rectal Cancer, Version 6.2020. J Natl Compr Canc Netw. 2020;18(7):806–15.CrossRefPubMed
18.
Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl4):iv22–iv40.CrossRefPubMed
19.
Francois Y, Nemoz CJ, Baulieux J, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999;17(8):2396.CrossRefPubMed
20.
Aschele C, Cionini L, Lonardi S, et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011;29(20):2773–80.CrossRefPubMed
21.
Gérard JP, Azria D, Gourgou-Bourgade S, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30(36):4558–65.CrossRefPubMed
22.
Rödel C, Graeven U, Fietkau R, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the german CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16(8):979–89.CrossRefPubMed
23.
Deng Y, Chi P, Lan P, et al. Modified FOLFOX6 with or without Radiation Versus Fluorouracil and Leucovorin with Radiation in Neoadjuvant Treatment of locally advanced rectal Cancer: initial results of the chinese FOWARC multicenter, Open-Label, Randomized three-arm phase III trial. J Clin Oncol. 2016;34(27):3300–7.CrossRefPubMed
24.
Allegra CJ, Yothers G, O’Connell MJ et al. Neoadjuvant 5-FU or Capecitabine Plus Radiation with or without oxaliplatin in rectal Cancer patients: a phase III Randomized Clinical Trial. J Natl Cancer Inst 2015; 107(11).
25.
Ishihara S, Matsusaka S, Kondo K, et al. A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer (SHOGUN trial). Radiat Oncol. 2015;10:24.CrossRefPubMedPubMedCentral
26.
Kondo K, Matsusaka S, Ishihara S, et al. Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial). Radiother Oncol. 2019;134:199–203.CrossRefPubMed
27.
Hüttner FJ, Probst P, Kalkum E, et al. Addition of platinum derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III rectal Cancer: systematic review and Meta-analysis. J Natl Cancer Inst. 2019;111(9):887–902.CrossRefPubMedPubMedCentral
28.
De Felice F, Benevento I, Magnante AL, et al. Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis: oxaliplatin in neoadjuvant treatment for rectal cancer. BMC Cancer. 2017;17(1):325.CrossRefPubMedPubMedCentral
29.
Murono K, Tsuno NH, Kawai K, et al. SN-38 overcomes chemoresistance of colorectal cancer cells induced by hypoxia, through HIF1alpha. Anticancer Res. 2012;32(3):865–72.PubMed
30.
Okuno T, Kawai K, Hata K, et al. SN-38 Acts as a Radiosensitizer for Colorectal Cancer by inhibiting the Radiation-induced Up-regulation of HIF-1α. Anticancer Res. 2018;38(6):3323–31.CrossRefPubMed
31.
Sato T, Ozawa H, Hatate K, et al. A phase II trial of neoadjuvant preoperative chemoradiotherapy with S-1 plus irinotecan and radiation in patients with locally advanced rectal cancer: clinical feasibility and response rate. Int J Radiat Oncol Biol Phys. 2011;79(3):677–83.CrossRefPubMed
32.
Mehta VK, Cho C, Ford JM, et al. Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys. 2003;55(1):132–7.CrossRefPubMed
33.
Navarro M, Dotor E, Rivera F, et al. A phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66(1):201–5.CrossRefPubMed
34.
Willeke F, Horisberger K, Kraus-Tiefenbacher U, et al. A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Br J Cancer. 2007;96(6):912–7.CrossRefPubMedPubMedCentral
35.
Shin SJ, Kim NK, Keum KC, et al. Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer. Radiother Oncol. 2010;95(3):303–7.CrossRefPubMed
36.
Jung M, Shin SJ, Koom WS, et al. A randomized phase 2 study of Neoadjuvant Chemoradiaton Therapy with 5-Fluorouracil/Leucovorin or Irinotecan/S-1 in patients with locally advanced rectal Cancer. Int J Radiat Oncol Biol Phys. 2015;93(5):1015–22.CrossRefPubMed
37.
Zhu J, Liu A, Sun X, et al. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation with Capecitabine and Irinotecan guided by. J Clin Oncol. 2020;38(36):4231–9.CrossRefPubMedPubMedCentral
38.
Klautke G, Küchenmeister U, Foitzik T, et al. Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by pathologic complete response. Radiother Oncol. 2007;85(3):379–84.CrossRefPubMed
39.
Jin J, Tang Y, Hu C, et al. Multicenter, Randomized, Phase III Trial of short-term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in locally advanced rectal Cancer (STELLAR). J Clin Oncol. 2022;40(15):1681–92.CrossRefPubMedPubMedCentral
40.
De Felice F, Magnante AL, Musio D, et al. Diffusion-weighted magnetic resonance imaging in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Eur J Surg Oncol. 2017;43(7):1324–9.CrossRefPubMed
41.
Ciolina M, Caruso D, De Santis D, et al. Dynamic contrast-enhanced magnetic resonance imaging in locally advanced rectal cancer: role of perfusion parameters in the assessment of response to treatment. Radiol Med. 2019;124(5):331–8.CrossRefPubMed
Metadata
Title
Preoperative chemoradiotherapy using tegafur/uracil, oral leucovorin, and irinotecan (TEGAFIRI) followed by oxaliplatin-based chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: the study protocol for a phase II trial
Authors
Shinya Abe
Kazushige Kawai
Hiroaki Nozawa
Kazuhito Sasaki
Koji Murono
Shigenobu Emoto
Yuichiro Yokoyama
Hiroyuki Matsuzaki
Yuzo Nagai
Yuichiro Yoshioka
Takahide Shinagawa
Hirofumi Sonoda
Yoko Yamamoto
Koji Oba
Soichiro Ishihara
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10941-z

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer

Correction

Correction: Shikonin inhibits cancer cell cycling by targeting Cdc25s

Research

Survival of cervical cancer patients at Moi teaching and Referral Hospital, Eldoret in western Kenya

Research

Colon and rectal cancer treatment patterns and their associations with clinical, sociodemographic and lifestyle characteristics: analysis of the Australian 45 and Up Study cohort

Review

Promising preclinical patient-derived organoid (PDO) and xenograft (PDX) models in upper gastrointestinal cancers: progress and challenges

Research

Biomarker analysis for patients with pancreatic cancer treated with nanoliposomal irinotecan plus 5-fluorouracil/leucovorin
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits