Rectal cancer

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Note: the page has (neo-)adjuvant regimens specific to rectal cancer. Please see the colon cancer page for adjuvant regimens specific to colon cancer (e.g., adjuvant CapeOx) and the colorectal cancer page for regimens intended more generically for colorectal cancer.
Last updated on 2024-12-02:23 regimens on this page
51 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2024: Scott et al. Management of Locally Advanced Rectal Cancer: ASCO Guideline EuroPMC
==ESMO==
*2018: Glynne-Jones et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2017: Glynne-Jones et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2013: Glimelius et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Glimelius et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Glimelius & Oliveira. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Glimelius & Oliveira. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2007: Glimelius. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2005: Tveit & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer EuroPMC
**2003: Tveit. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer EuroPMC
==French Intergroup==
*2017: Gérard et al. Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO) EuroPMC
==NCCN==
*NCCN Guidelines - Rectal Cancer
**2015: Benson et al. Rectal Cancer, Version 2.2015 EuroPMC
**2009: Engstrom et al. NCCN Clinical Practice Guidelines in Oncology: rectal cancer. EuroPMC
==SIOG==
*2018: Montroni et al. Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer EuroPMC
=Neoadjuvant therapy=
==Capecitabine & RT==
Capecitabine & RT: Capecitabine & Radiation Therapy
===Regimen variant #1, interrupted capecitabine, 1600 mg/m2/day, 4500 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gérard et al. 2010 (ACCORD 12/0405 PRODIGE 2)	2005-2008 	Phase 3 (C)	CapeOx & RT	Might have lower pCR rate
Note: adjuvant therapy was not specified. Treatment is assumed to start on a Monday.
====Chemotherapy====
*Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*Surgery
===Regimen variant #2, interrupted capecitabine, 1600 mg/m2/day, 5000 cGy===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Conroy et al. 2021 (UNICANCER-PRODIGE 23)	2012-2017 	Non-randomized part of phase 3 RCT	 	
François et al. 2022 	2016-2019 	Phase 3 (C) 	RT; 5 x 5 	Inconclusive whether non-inferior R0 resection rate
Note: Treatment is assumed to start on a Monday.
====Preceding treatment====
*UNICANCER-PRODIGE 23: Neoadjuvant FOLFIRINOX versus no neoadjuvant chemotherapy
====Chemotherapy====
*Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*UNICANCER-PRODIGE 23: TME, then adjuvant mFOLFOX6
*François et al. 2022: Surgery
===Regimen variant #3, interrupted capecitabine, 1650 mg/m2/day, 4500 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Schmoll et al. 2020 (PETACC 6)	2008-2011 	Phase 3 (C)	CapeOx & RT	Did not meet primary endpoint of DFS36DFS36: 76.5% vs 75.8%(HR 0.98, 95% CI 0.78-1.22)
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*Surgery, then adjuvant capecitabine
===Regimen variant #4, continuous capecitabine, 1650 mg/m2/day, 4500 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Hofheinz et al. 2012 (Rektum-III) 	2002-2007 	Phase 3 (E-RT-switch-ic)	5-FU & RT 	Non-inferior OS (primary endpoint)OS60: 76% vs 67%	
Park et al. 2011 (AMC Rectal Pre Vs Post 2004)	2004-2006 	Phase 3 (E-switch-ic) 	Capecitabine & RT; adjuvant	Did not meet primary endpoint of DFS36 	Better sphincter preservation
O'Connell et al. 2014 (NSABP R-04) 	2004-2010 	Phase 3 (E-switch-ic) 	1. 5-FU & RT 	Did not meet primary endpoint of LRC 	Similar toxicity
O'Connell et al. 2014 (NSABP R-04) 	2004-2010 	Phase 3 (E-switch-ic) 	2. CapeOx & RT 3. FUOX & RT	Did not meet primary endpoint of LRC 	Better toxicity
Valentini et al. 2016 (INTERACT) 	2005-2013 	Phase 3 (C) 	CapeOx & RT 	Did not meet efficacy endpoints 	Better toxicity
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 38
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions/4500 cGy), with boost depending on stage
5.5-week course
====Subsequent treatment====
*Surgery, then adjuvant capecitabine
===Regimen variant #5, interrupted capecitabine, 1650 mg/m2/day, 5000 cGy===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zhu et al. 2020 (CinClare)	2015-2017 	Phase 3 (C)	See link 	See link
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*Neoadjuvant CapeOx x 1, then TME, then adjuvant CapeOx x 5
===Regimen variant #6, interrupted capecitabine, 1650 mg/m2/day, 5040 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Schmoll et al. 2020 (PETACC 6)	2008-2011 	Phase 3 (C)	CapeOx & RT	Did not meet primary endpoint of DFS36DFS36: 76.5% vs 75.8%(HR 0.98, 95% CI 0.78-1.22)
Note: Treatment starts on a Monday.
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (5040 cGy total in 28 fractions)
5.5-week course
====Subsequent treatment====
*Surgery, then adjuvant capecitabine
===References===
# ACCORD 12: Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-PRODIGE 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. Epub 2010 Mar 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00227747
## Update: Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Seitz JF, Bedenne L, Juzyna B, Conroy T. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012 Dec 20;30(36):4558-65. Epub 2012 Oct 29. link to original article EuroPMC
# AMC Rectal Pre Vs Post 2004: Park JH, Yoon SM, Yu CS, Kim JH, Kim TW, Kim JC. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer. 2011 Aug 15;117(16):3703-12. Epub 2011 Feb 15. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT01186081
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
# NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00058474
## Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. 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 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article EuroPMC
#INTERACT: Valentini V, Gambacorta MA, Cellini F, Aristei C, Coco C, Barbaro B, Alfieri S, D'Ugo D, Persiani R, Deodato F, Crucitti A, Lupattelli M, Mantello G, Navarria F, Belluco C, Buonadonna A, Boso C, Lonardi S, Caravatta L, Barba MC, Vecchio FM, Maranzano E, Genovesi D, Doglietto GB, Morganti AG, La Torre G, Pucciarelli S, De Paoli A. The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer. Radiother Oncol. 2019 May;134:110-118. Epub 2019 Feb 7. link to original article EuroPMC NCT01653301
#CinClare: Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02605265
# PETACC 6: Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00766155
# UNICANCER-PRODIGE 23: Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. 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 May;22(5):702-715. Epub 2021 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01804790
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Borg C, Etienne PL, Rio E, Rullier E, Juzyna B, Castan F, Conroy T. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis. Eur J Cancer. 2023 Jun;186:151-165. Epub 2023 Mar 24. link to original article EuroPMC
##Update: Conroy T, Castan F, Etienne PL, Rio E, Mesgouez-Nebout N, Evesque L, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Boilève A, Delaye M, Gourgou S, Pezzella V, Borg C. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial. Ann Oncol. 2024 Oct;35(10):873-881. Epub 2024 Jul 8. link to original article EuroPMC
# STELLARrectal: Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. 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 May 20;40(15):1681-1692. Epub 2022 Mar 9. link to original article link to PMC article NCT02533271 EuroPMC
#CONVERTrectal: Mei WJ, Wang XZ, Li YF, Sun YM, Yang CK, Lin JZ, Wu ZG, Zhang R, Wang W, Li Y, Zhuang YZ, Lei J, Wan XB, Ren YK, Cheng Y, Li WL, Wang ZQ, Xu DB, Mo XW, Ju HX, Ye SW, Zhao JL, Zhang H, Gao YH, Zeng ZF, Xiao WW, Zhang XP, Zhang X, Xie E, Feng YF, Tang JH, Wu XJ, Chen G, Li LR, Lu ZH, Wan DS, Bei JX, Pan ZZ, Ding PR. Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial. Ann Surg. 2023 Apr 1;277(4):557-564. Epub 2022 Dec 20. link to original article link to PMC article EuroPMC NCT02288195
# François E, De Bari B, Ronchin P, Nouhaud E, Martel-Lafay I, Artru P, Clavere P, Vendrely V, Boige V, Gargot D, Lemanski C, De Sousa Carvalho N, Gal J, Pernot M, Magné N. Comparison of short course radiotherapy with chemoradiotherapy for locally advanced rectal cancers in the elderly: A multicentre, randomised, non-blinded, phase 3 trial. Eur J Cancer. 2023 Feb;180:62-70. Epub 2022 Nov 28. link to original article EuroPMC
#PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC NCT01515787
##PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC
==Capecitabine, Sorafenib, RT==
Capecitabine, Sorafenib, RT: Capecitabine, Sorafenib, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
von Moos et al. 2017 (SAKK 41/08)	2009-03 to 2013-05 	Phase 1/2
====Biomarker eligibility criteria====
*KRAS-mutation
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 33
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO once per day
====Radiotherapy====
*Concurrent radiation therapy, 4500 cGy total
5-week course
====Subsequent treatment====
*Surgery
===References===
# SAKK 41/08: von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K; Swiss Group for Clinical Cancer Research. Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer. 2018 Jan;89:82-89. Epub 2017 Dec 11. link to original article EuroPMC
==CapeOx==
CapeOX: Capecitabine & OXaliplatin
===Regimen variant #1, 4 cycles===
Study 	Dates of enrollment	Evidence
Chua et al. 2010	2001-2005 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Neoadjuvant Capecitabine & RT, then TME
===Regimen variant #2, 6 cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bahadoer et al. 2020 (RAPIDO)	2011-2016 	Phase 3 (E-switch-ic)	See link 	See link
====Preceding treatment====
*Neoadjuvant RT; 5 x 500 cGy
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for 6 cycles
====Subsequent treatment====
*TME
===References===
# Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. Epub 2010 Jan 25. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00220051
#RAPIDO: Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. 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 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01558921
==CapeOx, Camrelizumab, SCRT==
CapeOX, Camrelizumab, SCRT: Capecitabine, OXaliplatin, Camrelizumab, Short-Course Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lin et al. 2024 (UNION)	2021-07 to 2023-03 	Phase 3 (E-esc)	Capecitabine & LCRT, then CapeOx	Higher pCR rate (primary endpoint)pCR rate: 39.8% vs 15.3%
====Chemotherapy====
*Capecitabine (Xeloda) as follows:
**Cycles 2 & 3: 1000 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) as follows:
**Cycles 2 & 3: 130 mg/m2 IV over 60 minutes once on day 1
====Immunotherapy====
*Camrelizumab (AiRuiKa) as follows:
**Cycles 2 & 3: 200 mg/m2 IV once on day 1
====Radiotherapy====
*RT as follows:
**Cycle 1: 500 cGy per day on days 1 to 5
5-day course, then 21-day cycle for 2 cycles
====Subsequent treatment====
*TME
===References===
# UNION: Lin ZY, Zhang P, Chi P, Xiao Y, Xu XM, Zhang AM, Qiu XF, Wu JX, Yuan Y, Wang ZN, Qu XJ, Li X, Nie X, Yang M, Cai KL, Zhang WK, Huang Y, Sun Z, Hou ZG, Ma C, Cheng FZ, Tao KX, Zhang T. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial. Ann Oncol. 2024 Oct;35(10):882-891. Epub 2024 Jul 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04928807
==CapeOx, Cetuximab, RT==
CapeOX, Cetuximab, RT: Capecitabine, OXaliplatin, Cetuximab, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Leichman et al. 2017 (SWOG S0713)	2009-02 to 2013-04 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day on Monday to Friday
*Oxaliplatin (Eloxatin) as follows:
**Cycle 1: 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
**Cycle 2: 50 mg/m2 IV once per day on days 1, 8, 22, 29
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once per day on days 8, 15, 22, 29
**Cycle 2: 250 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*RT as follows:
**Cycle 2: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions)
35-day cycle for 2 cycles
====Subsequent treatment====
*TME
===References===
# SWOG S0713: Leichman CG, McDonough SL, Smalley SR, Billingsley KG, Lenz HJ, Beldner MA, Hezel AF, Velasco MR, Guthrie KA, Blanke CD, Hochster HS. Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713. Clin Colorectal Cancer. 2018 Mar;17(1):e121-e125. Epub 2017 Oct 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00686166
==CapIriRT==
CapIriRT: Capecitabine, Irinotecan, Radiation Therapy
===Regimen variant #1, 65 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zhu et al. 2020 (CinClare)	2015-2017 	Phase 3 (E-switch-ic)	See link 	See link
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
====Biomarker eligibility criteria====
*UGT1A1*1*28 genotype
====Chemotherapy====
*Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
*Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*Neoadjuvant CAPIRI x 1, then TME, then adjuvant CapeOx x 5
===Regimen variant #2, 80 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zhu et al. 2020 (CinClare)	2015-2017 	Phase 3 (E-switch-ic)	See link 	See link
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
====Biomarker eligibility criteria====
*UGT1A1*1*1 genotype
====Chemotherapy====
*Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
*Irinotecan (Camptosar) 80 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
====Subsequent treatment====
*Neoadjuvant CAPIRI x 1, then TME, then adjuvant CapeOx x 5
===References===
#CinClare: Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02605265
==Fluorouracil & RT==
Fluorouracil & RT: Fluorouracil & Radiation Therapy
===Regimen variant #1, continuous===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Ngan et al. 2012 (TROG 01.014) 	2001-2006 	Phase 3 (C)	Short-course RT 	Did not meet primary endpoint of LR rate at 36 mo	Similar toxicity
Aschele et al. 2011 (STAR-01) 	2003-2008 	Phase 3 (C)	FUOX & RT 	Did not meet primary endpoint of OS1 	Less toxic
O'Connell et al. 2014 (NSABP R-04)	2004-2010 	Phase 3 (C)	1. Capecitabine & RT 	Did not meet primary endpoint of LRC 	Similar toxicity
O'Connell et al. 2014 (NSABP R-04)	2004-2010 	Phase 3 (C)	2. CapeOx & RT 3. FUOX & RT	Did not meet primary endpoint of LRC 	Better toxicity
1Reported efficacy for STAR-01 is based on the 2016 update.
====Chemotherapy====
*Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion until the end of radiation, started on day 1
====Radiotherapy====
*Concurrent radiation therapy, 180 cGy for 25 fractions (4500 cGy), with boost depending on stage
5-week course
====Subsequent treatment====
*STAR-01: Surgery, preferably TME, then adjuvant fluourouracil-based therapy
*NSABP R-04: Surgery
===Regimen variant #2, intermittent===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sauer et al. 2004 (CAO/ARO/AIO-94)	1995-2002 	Phase 3 (E-switch-ic)	5-FU & RT; adjuvant	Lower five-year cumulative incidence of local relapse (secondary endpoint)
Hofheinz et al. 2012 (Rektum-III) 	2002-2007 	Phase 3 (C) 	Capecitabine & RT 	Non-inferior OS
Rödel et al. 2012 (CAO/ARO/AIO-04)	2006-2010 	Phase 3 (C) 	FUOX & RT 	Seems to have lower pCR rate
====Chemotherapy====
*Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on days 1 & 29 (total dose: 10,000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy, 5040 cGy total
One course
====Subsequent treatment====
*CAO/ARO/AIO-94: TME, then adjuvant 5-FU
===References===
# CAO/ARO/AIO-94: Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. Epub 2012 Apr 23. link to original article EuroPMC
# STAR-01: Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. 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 Jul 10;29(20):2773-80. Epub 2011 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Abstract: Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 link to abstract
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
# CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00349076
## Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. 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 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article EuroPMC
##HRQoL analysis: Kosmala R, Fokas E, Flentje M, Sauer R, Liersch T, Graeven U, Fietkau R, Hohenberger W, Arnold D, Hofheinz RD, Ghadimi M, Ströbel P, Staib L, Grabenbauer GG, Folprecht G, Kirste S, Uter W, Gall C, Rödel C, Polat B; of the German Rectal Cancer Study Group. Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial. Eur J Cancer. 2021 Feb;144:281-290. Epub 2020 Dec 28. link to original article EuroPMC
# TROG 01.014: Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00351598
# NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00058474
## Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. 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 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article EuroPMC
#PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC NCT01515787
##PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC
==FOLFIRINOX==
FOLFIRINOX: FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Conroy et al. 2021 (UNICANCER-PRODIGE 23)	2012-2017 	Phase 3 (E-esc)	No neoadjuvant chemotherapy	Seems to have higher DFS36 (primary endpoint)DFS36: 76% vs 69%(sHR 0.69, 95% CI 0.49-0.97)Higher DFS84 (secondary endpoint)DFS84: 67.6% vs 62.5%(RMST 5.73 mo, 95% CI 0.05-11.41)Longer OS (secondary endpoint)OS84: 81.9% vs 76.1%(RMST 4.37 mo, 95% CI 0.35-8.38)
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third
*Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given second
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 6 cycles
====Subsequent treatment====
*Neoadjuvant Capecitabine & RT
===References===
# UNICANCER-PRODIGE 23: Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. 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 May;22(5):702-715. Epub 2021 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01804790
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Borg C, Etienne PL, Rio E, Rullier E, Juzyna B, Castan F, Conroy T. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis. Eur J Cancer. 2023 Jun;186:151-165. Epub 2023 Mar 24. link to original article EuroPMC
##Update: Conroy T, Castan F, Etienne PL, Rio E, Mesgouez-Nebout N, Evesque L, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Boilève A, Delaye M, Gourgou S, Pezzella V, Borg C. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial. Ann Oncol. 2024 Oct;35(10):873-881. Epub 2024 Jul 8. link to original article EuroPMC
==mFOLFOX6==
mFOLFOX6: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Schrag et al. 2023 (PROSPECTrectal)	2012-06 to 2018-12 	Phase 3 (E-switch-ooc)	1a. Capecitabine & RT1b. 5-FU & RT	Non-inferior DFS (primary endpoint)DFS60: 80.8% vs 78.6%(HR 0.92, 90.2% CI 0.74-1.14)
Note: this trial (PROSPECT) is labeled as PROSPECTrectal to avoid confusion with the one by the same name in prostate cancer.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 6 cycles
====Subsequent treatment====
*Surgery, then optional adjuvant mFOLFOX6 x 6
===References===
#PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC NCT01515787
##PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article EuroPMC
==FULV & RT==
FULV & RT: FluoroUracil, LeucoVorin, Radiation Therapy
===Regimen variant #1, 800/200 ("Nordic schedule")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Braendengen et al. 2008 (LARCS)	1996-2003 	Phase 3 (E-esc)	Radiotherapy	Might have higher OS60 (primary endpoint)OS60: 66% vs 53%
Note: reported efficacy is based on the 2018 update.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1, 2, 15, 16, 29, 30, given first, prior to RT
*Leucovorin (Folinic acid) 100 mg IV once per day on days 1 & 2, given second
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, total of 5000 cGy)
5-week course
====Subsequent treatment====
*Surgery, then adjuvant FULV x 8
===Regimen variant #2, 1625/100===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Roh et al. 2009 (NSABP R-03)	1993-1999 	Phase 3 (E-esc)	Adjuvant 5-FU & RT	Might have longer OS (co-primary endpoint)OS60: 74.5% vs 65.6%(HR 0.69, 95% CI 0.47-1.03)
====Preceding treatment====
*Neoadjuvant FULV x 1
====Chemotherapy====
*Fluorouracil (5-FU) 325 mg/m2 IV once per day on days 1 to 5, 29 to 33
*Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy, 5040 cGy
5-week course
====Subsequent treatment====
*Surgery, then adjuvant FULV x 4
===Regimen variant #3, 1750/100===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sainato et al. 2014 (I-CNR-RT) 	1992-2001 	Non-randomized part of phase 3 RCT	 	
Bosset et al. 2006 (EORTC 22921)	1993-2003 	Phase 3 (E-esc) 	Radiotherapy	Did not meet primary endpoint of OS1
Gérard et al. 2006 (FFCD 9203) 	1993-2003 	Phase 3 (E-esc) 	Radiotherapy	Did not meet primary endpoint of OS1
1These trials were negative for the primary endpoint of overall survival, but had much improved local control for the experimental arm.
====Chemotherapy====
*Fluorouracil (5-FU) 350 mg/m2 IV once per day on days 1 to 5, 29 to 33
*Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5, 29 to 33
====Radiotherapy====
*Concurrent radiation therapy, 4500 cGy
5-week course
====Subsequent treatment====
*FFCD 9203 & EORTC 22921: Surgery, then adjuvant FULV x 2
*I-CNR-RT: Surgery, then adjuvant FULV versus no further treatment
===Regimen variant #4, 2800/400===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Deng et al. 2016 (FOWARC)	2010-2015 	Phase 3 (C)	1. mFOLFOX6 	Did not meet primary endpoint of DFS361
Deng et al. 2016 (FOWARC)	2010-2015 	Phase 3 (C)	2. mFOLFOX6 & RT	Did not meet primary endpoint of DFS361
1Reported efficacy is based on the 2019 update.
Note: this regimen is stated to be based on the de Gramont regimen in the manuscript, although the details are different than those in de Gramont et al. 2000.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
14-day cycle for 5 cycles
====Radiotherapy====
*Concurrent radiation therapy given during cycles 2 to 4: 1.8 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions over 5 to 6 weeks and a total dose of 4600 to 5040 cGy
6-week course
====Subsequent treatment====
*Surgery, then adjuvant FULV x 7
===References===
# FFCD 9203: Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00296608
# EORTC 22921: Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. Erratum in: N Engl J Med. 2007 Aug 16;357(7):728. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002523
## Update: Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. Epub 2014 Jan 17. link to original article EuroPMC
# LARCS: Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##HRQoL analysis: Brændengen M, Tveit KM, Hjermstad MJ, Johansson H, Berglund Å, Brandberg Y, Glimelius B. Health-related quality of life (HRQoL) after multimodal treatment for primarily non-resectable rectal cancer Long-term results from a phase III study. Eur J Cancer. 2012 Apr;48(6):813-819. link to original article link to EuroPMC
## Update: Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. link to original article EuroPMC
# NSABP R-03: Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009 Nov 1;27(31):5124-30. Epub 2009 Sep 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# I-CNR-RT: Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, Aristei C, Vidali C, Conti M, Galardi A, Ponticelli P, Friso ML, Iannone T, Osti FM, Manfredi B, Coppola M, Orlandini C, Cionini L. No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014 Nov;113(2):223-9. Epub 2014 Nov 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# FOWARC: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. 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 Sep 20;34(27):3300-7. Epub 2016 Aug 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01211210
## Update: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. link to original article link to PMC article EuroPMC
==FUOX & RT==
FUOX & RT: FluoroUracil, OXaliplatin, Radiation Therapy
===Regimen variant #1, 225/50===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
O'Connell et al. 2014 (NSABP R-04)	2004-2010 	Phase 3 (E-esc)	1. 5-FU & RT2. Capecitabine & RT	Did not meet primary endpoint of LRC	Worse toxicity
O'Connell et al. 2014 (NSABP R-04)	2004-2010 	Phase 3 (E-esc)	3. CapeOx & RT 	Did not meet primary endpoint of LRC	Similar toxicity
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
====Chemotherapy====
*Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 5625 mg/m2)
*Oxaliplatin (Eloxatin) 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy, 5040 cGy total
5.5-week course
====Subsequent treatment====
*Surgery
===Regimen variant #2, 225/60===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Aschele et al. 2011 (STAR-01)	2003-2008 	Phase 3 (E-esc)	Fluorouracil & RT	Did not meet primary endpoint of OS1	More toxic
1Reported efficacy is based on the 2016 update.
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
====Chemotherapy====
*Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over approximately 6 weeks, started on day 1
*Oxaliplatin (Eloxatin) 60 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*Concurrent radiation therapy, 5040 cGy total
6-week course
====Subsequent treatment====
*Surgery, preferably TME, then adjuvant fluourouracil-based therapy
===Regimen variant #3, 250/50===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rödel et al. 2012 (CAO/ARO/AIO-04)	2006-2010 	Phase 3 (E-esc)	Fluorouracil & RT	Seems to have higher pCR rate (secondary endpoint)
====Chemotherapy====
*Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 14 days, started on days 1 & 22 (total dose: 7000 mg/m2)
*Oxaliplatin (Eloxatin) 50 mg/m2 IV over 2 hours once per day on days 1, 8, 22, 29
====Radiotherapy====
*Concurrent radiation therapy, 5040 cGy total
One course
====Subsequent treatment====
*Surgery, then adjuvant FOLFOX
===References===
# STAR-01: Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. 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 Jul 10;29(20):2773-80. Epub 2011 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Abstract: Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 link to abstract
# CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00349076
## Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. 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 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article EuroPMC
##HRQoL analysis: Kosmala R, Fokas E, Flentje M, Sauer R, Liersch T, Graeven U, Fietkau R, Hohenberger W, Arnold D, Hofheinz RD, Ghadimi M, Ströbel P, Staib L, Grabenbauer GG, Folprecht G, Kirste S, Uter W, Gall C, Rödel C, Polat B; of the German Rectal Cancer Study Group. Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial. Eur J Cancer. 2021 Feb;144:281-290. Epub 2020 Dec 28. link to original article EuroPMC
# NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00058474
## Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. 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 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article EuroPMC
==mFOLFOX6 & RT==
mFOLFOX6 & RT: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin and Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Deng et al. 2016 (FOWARC)	2010-2015 	Phase 3 (E-esc)	1. FULV & RT	Did not meet primary endpoint of DFS361
Deng et al. 2016 (FOWARC)	2010-2015 	Phase 3 (E-esc)	2. mFOLFOX6 	Did not meet primary endpoint of DFS361
1Reported efficacy is based on the 2019 update.
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m2)
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 4 to 6 cycles
====Radiotherapy====
*Concurrent radiation therapy given before or after surgery at physician discretion: 180 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions, for a total dose of 4600 to 5040 cGy
5- to 6-week course
====Subsequent treatment====
*Surgery, then adjuvant mFOLFOX6 x 6 to 8
===References===
# FOWARC: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. 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 Sep 20;34(27):3300-7. Epub 2016 Aug 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01211210
## Update: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. link to original article link to PMC article EuroPMC
==Radiation therapy==
RT: Radiation Therapy
===Regimen variant #1, 2500 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cedermark et al. 1997 (Swedish Rectal Cancer Trial) 	1987-1990 	Phase 3 (E-esc) 	Surgery alone 	Longer OS
Kapiteijn et al. 2001 	1996-1999 	Phase 3 (E-esc) 	Surgery alone 	Lower local recurrence rate
Sebag-Montefiore et al. 2009 (MRC CR07; NCIC-CTG CO.16)	1998-2005 	Phase 3 (C) 	Selective postoperative 5-FU & RT	Seems to have longer DFS
Bujko et al. 2016 (Polish II) 	2008-2014 	Phase 3 (E-switch-ic)	FULV & RT 	Might have higher R0 resection rate (primary endpoint)
Bahadoer et al. 2020 (RAPIDO) 	2011-2016 	Phase 3 (E-switch-ic)	See link 	See link
====Radiotherapy====
*Radiation therapy, 500 cGy once per day for a total of 5 fractions (total dose: 2500 cGy)
5-day course
====Subsequent treatment====
*Swedish Rectal Cancer Trial, Kapiteijn et al. 2001, NCIC-CTG CO.16: Surgery
*Polish II: Neoadjuvant FOLFOX4 x 3, then Surgery
*RAPIDO: Neoadjuvant CapeOx x 6 or FOLFOX4 x 9, then Surgery
===Regimen variant #2, 4000 cGy===
Historic variant
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Oates et al. 1996	1981-1989 	Phase 3 (E-esc)	Surgery alone	Seems to have longer DFS
====Radiotherapy====
*Radiation therapy, 200 cGy x 20 fractions (total dose: 4000 cGy)
4-week course
====Subsequent treatment====
*Surgery
===Regimen variant #3, 5000 cGy===
Historic variant
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Braendengen et al. 2008 (LARCS)	1996-2003 	Phase 3 (C)	FULV/FULV & RT	Might have lower OS60
====Radiotherapy====
*Radiation therapy, 200 cGy x 25 fractions (total dose: 5000 cGy)
5-week course
====Subsequent treatment====
*Surgery
===References===
# Oates GD, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet. 1996 Dec 14;348(9042):1605-10. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Swedish Rectal Cancer Trial: Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N; Swedish Rectal Cancer Trial investigators. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. link to original article EuroPMC
## Update: Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. link to original article EuroPMC
# Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. link to original article EuroPMC
# LARCS: Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##HRQoL analysis: Brændengen M, Tveit KM, Hjermstad MJ, Johansson H, Berglund Å, Brandberg Y, Glimelius B. Health-related quality of life (HRQoL) after multimodal treatment for primarily non-resectable rectal cancer Long-term results from a phase III study. Eur J Cancer. 2012 Apr;48(6):813-819. link to original article link to EuroPMC
## Update: Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. link to original article EuroPMC
# MRC CR07; NCIC-CTG CO.16: Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00003422
# Polish II: Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. Epub 2016 Feb 15. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00833131
## Update: Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spałek M, Polkowski W, Jankiewicz M, Styliński R, Bębenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Żelazowska-Omiotek U, Kępka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kładny J, Majewski A, Kapuściński W, Suwiński R, Bujko K; Polish Colorectal Study Group. Long-course preoperative chemoradiation vs 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019 Aug 1;30(8):1298-1303. Epub 2019 Jun 13. link to original article EuroPMC
#RAPIDO: Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. 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 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01558921
=Adjuvant chemotherapy=
==Capecitabine monotherapy==
===Regimen variant #1, 2000 mg/m2/day x 6===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Schmoll et al. 2020 (PETACC 6)	2008-2011 	Phase 3 (C)	CapeOx 	Did not meet primary endpoint of DFS36
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant capecitabine & RT, then surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 15
21-day cycle for 6 cycles
===Regimen variant #2, 2500 mg/m2/day x 5===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hofheinz et al. 2012 (Rektum-III)	2002-2007 	Phase 3 (E-RT-switch-ic)	Fluorouracil	Non-inferior OS (primary endpoint)OS60: 76% vs 67%
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant capecitabine & RT, then surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 5 cycles
===Regimen variant #3, 2500 mg/m2/day x 8===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Breugom et al. 2014 (SCRIPT)	2000-2013 	Phase 3 (E-esc)	Observation	Did not meet primary endpoint of OS
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 8 cycles
===References===
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
# SCRIPT: Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN36266738
# PETACC 6: Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00766155
==Fluorouracil monotherapy==
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hofheinz et al. 2012 (Rektum-III)	2002-2007 	Phase 3 (C)	Capecitabine	Non-inferior OS
====Preceding treatment====
*Neoadjuvant 5-FU & RT, then surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1 to 5
28-day cycle for 4 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Rödel et al. 2012 (CAO/ARO/AIO-04)	2006-2010 	Phase 3 (C)	FOLFOX 	Seems to have shorter DFS1
1Reported efficacy is based on the 2015 update.
====Preceding treatment====
*Neoadjuvant 5-FU & RT, then surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1 to 5, 29
1-month cycle for 4 cycles
===References===
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
# CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00349076
## Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. 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 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article EuroPMC
##HRQoL analysis: Kosmala R, Fokas E, Flentje M, Sauer R, Liersch T, Graeven U, Fietkau R, Hohenberger W, Arnold D, Hofheinz RD, Ghadimi M, Ströbel P, Staib L, Grabenbauer GG, Folprecht G, Kirste S, Uter W, Gall C, Rödel C, Polat B; of the German Rectal Cancer Study Group. Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial. Eur J Cancer. 2021 Feb;144:281-290. Epub 2020 Dec 28. link to original article EuroPMC
==FULV==
FULV: 5-FU & LeucoVorin
===Regimen variant #1, 500/500===
Historic variant
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wolmark et al. 2000 (NSABP R-02)	1987-1992 	Phase 3 (C)	FULV & RT 	Did not meet primary endpoint of OS60
Note: male patients were also randomized to MOF or MOF & RT.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, given 1 hour after leucovorin
*Leucovorin (Folinic acid) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for 6 cycles
===Regimen variant #2, 1000/120 ("Nordic regimen")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Breugom et al. 2014 (PROCTOR)	2000-2013 	Phase 3 (E-esc)	Observation	Did not meet primary endpoint of OS
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have been used as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 2, given first (total dose per cycle: 1000 mg/m2)
*Leucovorin (Folinic acid) 60 mg/m2 IV once per day on days 1 & 2, given second (total dose per cycle: 120 mg/m2)
14-day cycle for 12 cycles
===Regimen variant #3, 1900/100===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hong et al. 2014 (ADORE)	2008-2012 	Randomized Phase 2 (C)	FOLFOX 	Seems to have lower DFS36 (primary endpoint)DFS36: 62.9% vs 71.6%(HR 1.52, 95% CI 1.006-2.33)
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
====Chemotherapy====
*Fluorouracil (5-FU) 380 mg/m2 IV bolus once per day on days 1 to 5 (total dose per cycle: 1900 mg/m2)
*Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m2)
28-day cycle for 4 cycles
===Regimen variant #4, 2125/100 ("Mayo regimen")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Delbaldo et al. 2015 (R98) 	1999-2005 	Phase 3 (C) 	FOLFIRI 	Did not meet primary endpoint of DFS
Breugom et al. 2014 (PROCTOR)	2000-2013 	Phase 3 (E-esc)	Observation	Did not meet primary endpoint of OSOS60: 80.4% vs 79.2%(HR 0.93, 95% CI 0.61-1.39)
Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*PROCTOR: Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
====Chemotherapy====
*Fluorouracil (5-FU) 425 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 2125 mg/m2)
*Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m2)
4- to 5-week cycle for 6 cycles
===References===
# NSABP R-02: Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# ADORE: Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. 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 Oct;15(11):1245-53. Epub 2014 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00807911
## Update: Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. link to original article EuroPMC
# PROCTOR: Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN36266738
# R98: Delbaldo C, Ychou M, Zawadi A, Douillard JY, André T, Guerin-Meyer V, Rougier P, Dupuis O, Faroux R, Jouhaud A, Quinaux E, Buyse M, Piedbois P; AERO; GERCOR; FNCLCC; FFCD. Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial. Ann Oncol. 2015 Jun;26(6):1208-15. Epub 2015 Mar 3. link to original article EuroPMC
==mFOLFOX6==
mFOLFOX6: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen variant #1, with 5-FU bolus, 8 cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hong et al. 2014 (ADORE)	2008-2012 	Randomized Phase 2 (E-esc)	FULV 	Seems to have higher DFS36 (primary endpoint)DFS36: 71.6% vs 62.9%(HR 0.66, 95% CI 0.43-0.994)
====Preceding treatment====
*Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once on day 1, given first
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 8 cycles
===Regimen variant #2, no 5-FU bolus, 8 cycles===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rödel et al. 2012 (CAO/ARO/AIO-04)	2006-2010 	Phase 3 (E-esc)	Fluorouracil	Seems to have longer DFS1 (primary endpoint)DFS36: 75.95% vs 71.2%(HR 0.79, 95% CI 0.64-0.98)
1Reported efficacy is based on the 2015 update.
====Preceding treatment====
*Neoadjuvant FUOX & RT, then surgery
====Chemotherapy====
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third (total dose per cycle: 2400 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second
*Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 8 cycles
===Regimen variant #3, 12 cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Chakravarthy et al. 2019 (ECOG E5204)	2006-2009 	Phase 3 (C)	mFOLFOX6-B	Did not meet primary endpoint of OSOS60: 88.3% vs 83.7%
====Preceding treatment====
*Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 12 cycles
===References===
# ADORE: Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. 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 Oct;15(11):1245-53. Epub 2014 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00807911
## Update: Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. link to original article EuroPMC
# CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00349076
## Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. 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 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article EuroPMC
##HRQoL analysis: Kosmala R, Fokas E, Flentje M, Sauer R, Liersch T, Graeven U, Fietkau R, Hohenberger W, Arnold D, Hofheinz RD, Ghadimi M, Ströbel P, Staib L, Grabenbauer GG, Folprecht G, Kirste S, Uter W, Gall C, Rödel C, Polat B; of the German Rectal Cancer Study Group. Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial. Eur J Cancer. 2021 Feb;144:281-290. Epub 2020 Dec 28. link to original article EuroPMC
#ECOG E5204: Chakravarthy AB, Zhao F, Meropol NJ, Flynn PJ, Wagner LI, Sloan J, Diasio RB, Mitchell EP, Catalano P, Giantonio BJ, Catalano RB, Haller DG, Awan RA, Mulcahy MF, O'Brien TE, Santala R, Cripps C, Weis JR, Atkins JN, Leichman CG, Petrelli NJ, Sinicrope FA, Brierley JD, Tepper JE, O'Dwyer PJ, Sigurdson ER, Hamilton SR, Cella D, Benson AB 3rd. Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204). Oncologist. 2020 May;25(5):e798-e807. Epub 2019 Dec 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00303628
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Oki et al. 2016 (ACTS-RC)	2006-2009 	Phase 3 (E-switch-ic)	UFT 	Seems to have longer RFS (primary endpoint)RFS60: 66.4% vs 61.7%(HR 0.77, 95% CI 0.63-0.96)
Note: these patients did not receive preoperative therapy.
====Preceding treatment====
*Curative resection for stage II or stage III rectal cancer, within 49 days
====Chemotherapy====
*Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
**Less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
**BSA 1.25 to 1.5 m2: 50 mg PO twice per day on days 1 to 28
**BSA 1.5 or greater m2: 60 mg PO twice per day on days 1 to 28
42-day cycle for 9 cycles (1 year)
===References===
# ACTS-RC: Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN C000000385
==UFT monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hamaguchi et al. 2010 (NSAS-CC)	1996-2001 	Phase 3 (E-esc)	Observation	Seems to have longer OS (secondary endpoint)
Oki et al. 2016 (ACTS-RC) 	2006-2009 	Phase 3 (C) 	S-1 	Seems to have shorter RFSRFS60: 61.7% vs 66.4%(HR 1.30, 95% CI 1.04-1.59)
Note: these patients did not receive preoperative therapy.
====Preceding treatment====
*Curative resection for stage II or stage III rectal cancer, within 49 days
====Chemotherapy====
*Tegafur and uracil (UFT) by the following BSA-based criteria:
**Less than 1.25 m2: 250 mg PO twice per day on days 1 to 5
**1.25 m2 or more: 300 mg PO twice per day on days 1 to 5
7-day cycle for 52 cycles
===References===
# NSAS-CC: Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011 Mar;67(3):587-96. Epub 2010 May 19. link to original article EuroPMC NCT00152230
# ACTS-RC: Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN C000000385
=Adjuvant chemoradiotherapy=
==Capecitabine & RT==
Capecitabine & RT: Capecitabine & Radiation Therapy
===Regimen variant #1, fully concurrent===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Feng et al. 2016 (CAMS rectal cancer 01)	2008-2014 	Phase 3 (C)	CapeOx & RT	Did not meet primary endpoint of DFSDFS36: 71.6% vs 73.9%
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 14, 22 to 36
====Radiotherapy====
*Concurrent radiation therapy, 4500 to 5040 cGy total in 25 to 28 fractions
5- to 5.5-week course
===Regimen variant #2, sandwich===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hofheinz et al. 2012 (Rektum-III)	2002-2007 	Phase 3 (E-RT-switch-ic)	5-FU & RT 	Non-inferior OS (primary endpoint)OS60: 76% vs 67%
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) as follows:
**Cycles 1 & 2: 1250 mg/m2 PO twice per day on days 1 to 14
**Cycle 3 (chemoradiation): 825 mg/m2 PO twice per day on days 1 to 38
**Cycles 4 to 6: 1250 mg/m2 PO twice per day on days 1 to 14
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3: 5040 cGy total
21-day cycle for 2 cycles, then 38-day course, then 21-day cycle for 3 cycles
===References===
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
# CAMS rectal cancer 01: Feng YR, Zhu Y, Liu LY, Wang WH, Wang SL, Song YW, Wang X, Tang Y, Liu YP, Ren H, Fang H, Zhang SP, Liu XF, Yu ZH, Li YX, Jin J. Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial. Oncotarget. 2016 May 3;7(18):25576-84. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00714077
==Fluorouracil & RT==
Fluorouracil & RT: Fluorouracil & Radiation Therapy
===Regimen variant #1, Bolus 5-FU (500 mg/m2), then CI 5-FU & RT, then Bolus 5-FU (450 mg/m2)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Connell et al. 1994 (INT 864751)	1986-1990 	Phase 3 (E-switch-ic)	5-FU & RT; bolus 	Longer OS
Smalley et al. 2006 (GI INT 0144) 	1994-2000 	Phase 3 (E-switch-ic)	1. 5-FU & RT; bolus	Not compared
Smalley et al. 2006 (GI INT 0144) 	1994-2000 	Phase 3 (E-switch-ic)	2. 5-FU & RT; CI 	Did not meet co-primary endpoints of OS/DFS
Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycles 1 & 2: 500 mg/m2 IV bolus once per day on days 1 to 5
**Cycle 3 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
**Cycles 4 & 5: 450 mg/m2 IV bolus once per day on days 1 to 5
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 8-week course, then 28-day cycle for 2 cycles
===Regimen variant #2, Bolus 5-FU (500 mg/m2), then CI 5-FU & RT, then Bolus 5-FU (500 mg/m2)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hofheinz et al. 2012 (Rektum-III)	2002-2007 	Phase 3 (C)	Capecitabine & RT	Non-inferior OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycles 1, 2, 4, 5: 500 mg/m2 IV bolus once per day on days 1 to 5
**Cycle 3 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3: 5040 cGy total
28-day cycle for 2 cycles, then one course, then 28-day cycle for 2 cycles
===Regimen variant #3, CI 5-FU, then CI 5-FU & RT, then CI 5-FU===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Smalley et al. 2006 (GI INT 0144)	1994-2000 	Phase 3 (E-switch-ic)	1. 5-FU & RT; bolus 	Did not meet co-primary endpoints of DFS/OS
Smalley et al. 2006 (GI INT 0144)	1994-2000 	Phase 3 (E-switch-ic)	2. 5-FU & RT; fully concurrent	Not compared
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycle 1: 300 mg/m2/day IV continuous infusion over 42 days, started on day 1 (total dose: 12,600 mg/m2)
**Cycle 2 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
**Cycle 3: 300 mg/m2/day IV continuous infusion over 56 days, started on day 1 (total dose: 16,800 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 2: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
10-week cycle for 3 cycles
===Regimen variant #4, bolus 5-FU, then bolus 5-FU & RT, then bolus 5-FU===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Connell et al. 1994 (INT 864751)	1986-1990 	Phase 3 (C)	5-FU & RT; bolus/CI 	Shorter OS
Tepper et al. 1997 (GI INT 0114) 	1990-1992 	Phase 3 (C)	1. FULV/FULV & RT 	Did not meet primary endpoint of DFS36
Tepper et al. 1997 (GI INT 0114) 	1990-1992 	Phase 3 (C)	2. Levamisole combination #1	Did not meet primary endpoint of DFS36
Tepper et al. 1997 (GI INT 0114) 	1990-1992 	Phase 3 (C)	3. Levamisole combination #2	Did not meet primary endpoint of DFS36
Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycles 1 & 2: 500 mg/m2 IV bolus once per day on days 1 to 5
**Cycle 3 (chemoradiation): 500 mg/m2 IV bolus 3 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
**Cycles 4 & 5: 450 mg/m2 IV bolus once per day on days 1 to 5
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 10-week course, then 28-day cycle for 2 cycles
===Regimen variant #5, fully concurrent===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fountzilas et al. 1999	1989-1997 	Phase 3 (C)	FULV/5-FU & RT	Did not meet primary endpoint of OS36
====Chemotherapy====
*Fluorouracil (5-FU)
====Radiotherapy====
*Radiation therapy
===References===
# INT 864751: O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GI INT 0114: Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
# Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Liaros A, Athanassiou E, Dombros N, Dervenis C, Basdanis G, Gamvros O, Souparis A, Briasoulis E, Samantas E, Kappas A, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 1999 Jun;10(6):671-6. link to original article EuroPMC
# GI INT 0144: Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, Fisher B, Rich TA, Martenson JA, Kugler JW, Benson AB 3rd, Haller DG, Mayer RJ, Atkins JN, Cripps C, Pedersen J, Periman PO, Tanaka MS Jr, Leichman CG, Macdonald JS. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006 Aug 1;24(22):3542-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002551
# Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01500993
==FULV/FULV & RT==
FULV/FULV & RT: FluoroUracil & LeucoVorin alternating with FluoroUracil, LeucoVorin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tepper et al. 1997 (GI INT 0114)	1990-1992 	Phase 3 (E-esc)	1. 5-FU & RT 	Did not meet primary endpoint of DFS36
Tepper et al. 1997 (GI INT 0114)	1990-1992 	Phase 3 (E-esc)	2. Levamisole combination #1	Did not meet primary endpoint of DFS36
Tepper et al. 1997 (GI INT 0114)	1990-1992 	Phase 3 (E-esc)	3. Levamisole combination #2	Did not meet primary endpoint of DFS36
Kalofonos et al. 2008 	1999-2004 	Phase 3 (C) 	IFL & RT 	Did not meet primary endpoint of OS36
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycles 1 & 2: 425 mg/m2 IV bolus once per day on days 1 to 5, given second
**Cycle 3 (chemoradiation): 400 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
**Cycles 4 & 5: 380 mg/m2 IV bolus once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) as follows:
**Cycles 1, 2, 4, 5: 20 mg/m2 IV bolus once per day on days 1 to 5, given first
**Cycle 3 (chemoradiation): 20 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 10-week course, then 28-day cycles for 2 cycles
===References===
# GI INT 0114: Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Kalofonos HP, Bamias A, Koutras A, Papakostas P, Basdanis G, Samantas E, Karina M, Misailidou D, Pisanidis N, Pentheroudakis G, Economopoulos T, Papadimitriou C, Skarlos DV, Pectasides D, Stavropoulos M, Bafaloukos D, Kardamakis D, Karanikiotis C, Vourli G, Fountzilas G; Hellenic Cooperative Oncology Group. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Eur J Cancer. 2008 Aug;44(12):1693-700. Epub 2008 Jul 17. link to original article EuroPMC
==Radiation therapy==
RT: Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fisher et al. 1988 (NSABP R-01)	1977-1986 	Phase 3 (E-esc)	1. MOF 	Not reported
Fisher et al. 1988 (NSABP R-01)	1977-1986 	Phase 3 (E-esc)	2. Observation 	Did not meet efficacy endpoints of DFS/OS
Krook et al. 1991 	1980-1986 	Phase 3 (C) 	Fluorouracil & RT	Shorter RFS
Amott et al. 1996 	1984-1989 	Phase 3 (E-esc)	Observation 	Lower local recurrence rate
Note: this regimen in this context is of historic interest.
====Preceding treatment====
*Surgery
====Radiotherapy====
*Radiation therapy, 4000 to 5040 cGy
4-week course
===References===
# NSABP R-01: Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. link to original article EuroPMC
# Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991 Mar 14;324(11):709-15. link to original article EuroPMC
# Amott SJ, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet. 1996 Dec 14;348(9042):1610-4. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# TROG 01.014: Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. link to original article EuroPMC NCT00351598
=Advanced or metastatic disease=
See the colorectal cancer page for colorectal cancer regimens.
Category:Rectal cancer regimens
Category:Disease-specific pages
Category:Colorectal cancers