Rectal cancer

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Section editor
Travis Zack, MD, PhD
University of California San Francisco
San Francisco, CA, USA
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Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

Last updated on 2024-09-06:
22 regimens on this page
50 variants on this page

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.


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.

ESMO


French Intergroup


NCCN


SIOG


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 inferior pCR rate

Note: adjuvant therapy was not specified. Treatment is assumed to start on a Monday.

Chemotherapy

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


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

Chemotherapy

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


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 DFS36

Chemotherapy

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


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 Superior 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
2. CapeOx & RT
3. FUOX & RT 		Did not meet primary endpoint of LRC Superior toxicity
Valentini et al. 2016 (INTERACT) 2005-2013 Phase 3 (C) CapeOx & RT Did not meet efficacy endpoints Superior toxicity

Chemotherapy

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


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

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


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 DFS36

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

References

  1. 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 PubMed NCT00227747
    1. 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 PubMed
  2. 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 PubMed NCT01186081
  3. 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 PubMed NCT01500993
  4. 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 PubMed NCT00058474
    1. 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 PubMed
  5. 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 PubMed NCT01653301
  6. 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 PubMed NCT02605265
  7. 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 PubMed NCT00766155
  8. 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 PubMed NCT01804790
    1. 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 PubMed
  9. 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 PubMed
  10. 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 PubMed NCT02288195
  11. 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 PubMed
  12. 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 PubMed NCT01515787
    1. 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 PubMed


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

Targeted therapy

Radiotherapy

5-week course

Subsequent treatment

References

  1. 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 PubMed


CapeOx

CapeOX: Capecitabine & OXaliplatin

Regimen variant #1, 4 cycles

Study Dates of enrollment Evidence
Chua et al. 2010 2001-2005 Phase 2

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment


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

21-day cycle for 6 cycles

Subsequent treatment

References

  1. 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 PubMed NCT00220051
  2. 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 PubMed NCT01558921


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

References

  1. 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 PubMed 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

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


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

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

References

  1. 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 PubMed 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
2. CapeOx & RT
3. FUOX & RT 		Did not meet primary endpoint of LRC Superior 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


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 Superior 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 inferior 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

One course

Subsequent treatment

  • CAO/ARO/AIO-94: TME, then adjuvant 5-FU

References

  1. 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 PubMed
    1. 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 PubMed
  2. 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 PubMed
    1. 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
  3. 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 PubMed NCT01500993
  4. 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 PubMed NCT00349076
    1. 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 PubMed
  5. 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 PubMed NCT00351598
  6. 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 PubMed NCT00058474
    1. 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 PubMed
  7. 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 PubMed NCT01515787
    1. 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 PubMed


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 superior DFS36 (primary endpoint)
DFS36: 76% vs 69%
(sHR 0.69, 95% CI 0.49-0.97)

Superior DFS84 (secondary endpoint)
DFS84: 67.6% vs 62.5%
(RMST 5.73 mo, 95% CI 0.05-11.41)

Superior OS (secondary endpoint)
OS84: 81.9% vs 76.1%
(RMST 4.37 mo, 95% CI 0.35-8.38)

Chemotherapy

14-day cycle for 6 cycles

Subsequent treatment

References

  1. 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 PubMed NCT01804790
    1. 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 PubMed


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 & RT
1b. 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

14-day cycle for 6 cycles

Subsequent treatment

References

  1. 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 PubMed NCT01515787
    1. 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 PubMed


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 superior OS60 (primary endpoint)
OS60: 66% vs 53%

Note: reported efficacy is based on the 2018 update.

Chemotherapy

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


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 superior 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

Radiotherapy

5-week course

Subsequent treatment


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

Radiotherapy

5-week course

Subsequent 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
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

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

References

  1. 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 PubMed NCT00296608
  2. 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 PubMed NCT00002523
    1. 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 PubMed
  3. 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 PubMed
    1. 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 PubMed
  4. 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 PubMed
  5. 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 PubMed
  6. 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 PubMed NCT01211210
    1. 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 PubMed


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 & RT
2. Capecitabine & RT 		Did not meet primary endpoint of LRC Inferior toxicity
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

Radiotherapy

5.5-week course

Subsequent treatment


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

Radiotherapy

6-week course

Subsequent treatment


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 superior pCR rate (secondary endpoint)

Chemotherapy

Radiotherapy

One course

Subsequent treatment

References

  1. 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 PubMed
    1. 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
  2. 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 PubMed NCT00349076
    1. 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 PubMed
  3. 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 PubMed NCT00058474
    1. 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 PubMed


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
2. mFOLFOX6 Did not meet primary endpoint of DFS361

1Reported efficacy is based on the 2019 update.

Chemotherapy

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

References

  1. 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 PubMed NCT01211210
    1. 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 PubMed


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 Superior OS
Kapiteijn et al. 2001 1996-1999 Phase 3 (E-esc) Surgery alone Superior 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 superior DFS
Bujko et al. 2016 (Polish II) 2008-2014 Phase 3 (E-switch-ic) FULV & RT Might have superior 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


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 superior DFS

Radiotherapy

4-week course

Subsequent treatment


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 inferior OS60

Radiotherapy

5-week course

Subsequent treatment

References

  1. 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 PubMed
  2. 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 PubMed
    1. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed
    1. 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 PubMed
  5. 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 PubMed NCT00003422
  6. 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 PubMed NCT00833131
    1. 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 PubMed
  7. 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 PubMed 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

Chemotherapy

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

Chemotherapy

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

Chemotherapy

21-day cycle for 8 cycles

References

  1. 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 PubMed NCT01500993
  2. 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 PubMed ISRCTN36266738
  3. 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 PubMed 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

Chemotherapy

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 inferior DFS1

1Reported efficacy is based on the 2015 update.

Preceding treatment

Chemotherapy

1-month cycle for 4 cycles

References

  1. 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 PubMed NCT01500993
  2. 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 PubMed NCT00349076
    1. 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 PubMed


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

Chemotherapy

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

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 inferior 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

Chemotherapy

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 OS

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

Chemotherapy

4- to 5-week cycle for 6 cycles

References

  1. 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 PubMed
  2. 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 PubMed NCT00807911
    1. 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 PubMed
  3. 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 PubMed ISRCTN36266738
  4. 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 PubMed


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 superior DFS36 (primary endpoint)
DFS36: 71.6% vs 62.9%
(HR 0.66, 95% CI 0.43-0.994)

Preceding treatment

Chemotherapy

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 superior 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

Chemotherapy

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 OS
OS60: 88.3% vs 83.7%

Preceding treatment

Chemotherapy

14-day cycle for 12 cycles

References

  1. 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 PubMed NCT00807911
    1. 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 PubMed
  2. 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 PubMed NCT00349076
    1. 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 PubMed
  3. 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 PubMed 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 superior 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

  1. 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 PubMed 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 superior OS (secondary endpoint)
Oki et al. 2016 (ACTS-RC) 2006-2009 Phase 3 (C) S-1 Seems to have inferior RFS

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

  1. 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 PubMed NCT00152230
  2. 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 PubMed 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 DFS
DFS36: 71.6% vs 73.9%

Preceding treatment

Chemotherapy

Radiotherapy

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

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

21-day cycle for 2 cycles, then 38-day course, then 21-day cycle for 3 cycles

References

  1. 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 PubMed NCT01500993
  2. 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 PubMed 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 Superior OS
Smalley et al. 2006 (GI INT 0144) 1994-2000 Phase 3 (E-switch-ic) 1. 5-FU & RT; bolus Not compared
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

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

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

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
2. 5-FU & RT; fully concurrent Not compared

Preceding treatment

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 Inferior OS
Tepper et al. 1997 (GI INT 0114) 1990-1992 Phase 3 (C) 1. FULV/FULV & RT Did not meet primary endpoint of DFS36
2. Levamisole combination #1 Did not meet primary endpoint of DFS36
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

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

Radiotherapy

References

  1. 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 PubMed
  2. 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 PubMed
    1. 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 PubMed content property of HemOnc.org
  3. 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 PubMed
  4. 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 PubMed NCT00002551
  5. 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 PubMed 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
2. Levamisole combination #1 Did not meet primary endpoint of DFS36
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

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

  1. 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 PubMed
    1. 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 PubMed
  2. 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 PubMed


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
2. Observation Did not meet efficacy endpoints of DFS/OS
Krook et al. 1991 1980-1986 Phase 3 (C) Fluorouracil & RT Inferior RFS
Amott et al. 1996 1984-1989 Phase 3 (E-esc) Observation Superior local recurrence rate

Note: this regimen in this context is of historic interest.

Preceding treatment

Radiotherapy

4-week course

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed NCT00351598


Advanced or metastatic disease

See the colorectal cancer page for colorectal cancer regimens.

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