Colon cancer

Back to Top
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. 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!
Note: This page has recently been reorganized, with regimens intended more generically for colorectal cancer being moved to a dedicated page. Now, this page has adjuvant regimens specific to colon cancer. Please see the rectal cancer page for (neo-)adjuvant regimens specific to rectal cancer.
*See the RAS wild-type page for biomarker-specific adjuvant regimens.
Last updated on 2024-09-06:11 regimens on this page
22 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.
==AIOM==
*2020: Salvatore et al. Management of patients with early-stage colon cancer: guidelines of the Italian Medical Oncology Association EuroPMC
==ASCO==
*2022: Baxter et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update EuroPMC
*2019: Lieu et al. Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline EuroPMC
==ESMO==
*2021: Yoshino et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer EuroPMC
*2020: Argilés et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines EuroPMC
**2009: van Cutsem & Oliveira. Primary colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up EuroPMC
**2008: van Cutsem & Oliveira. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up EuroPMC
**2007: van Cutsem. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up EuroPMC
**2005: van Cutsem & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer EuroPMC
**2001: ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer EuroPMC
*2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN Guidelines - Colon Cancer
**2024: Benson et al. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology EuroPMC
**2021: Benson et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. EuroPMC
**2017: Benson et al. Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology EuroPMC
**2014: Benson et al. Colon Cancer, Version 3.2014 EuroPMC
**2013: Benson et al. Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines. EuroPMC
**2011: Benson et al. Colon cancer. EuroPMC
**2009: Engstrom et al. NCCN Clinical Practice Guidelines in Oncology: colon cancer. EuroPMC
**2007: Engstrom et al. Colon cancer. EuroPMC
**2005: Engstrom et al. Colon cancer clinical practice guidelines in oncology. EuroPMC
**2003: Engstrom et al. Colon cancer. Clinical practice guidelines in oncology. link to PMC article EuroPMC
=Perioperative therapy=
==mFOLFOX6 (L-Leucovorin)==
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Morton et al. 2023 (FOxTROT)	2008-05-15 to 2016-12-23	Phase 3 (E-switch-ic)	mFOLFOX6; adjuvant	Seems to have higher rate of residual or recurrent disease within 2 years (primary endpoint)Rate: 16.9% vs 21.5%(RR 0.72, 95% CI 0.54-0.98)
Note: FOxTROT was a 2 x 2 factorial trial, with a sub-randomization to panitumumab, or not, for patients with KRASwt tumors. See paper for details.
===Neoadjuvant===
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
*Levoleucovorin (Fusilev) 175 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 3 cycles, followed by:
===Definitive===
====Local therapy====
*Surgery
===Adjuvant===
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
*Levoleucovorin (Fusilev) 175 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 9 cycles
===References===
#FOxTROT: Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. Epub 2023 Jan 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00647530
=Adjuvant therapy=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Twelves et al. 2005 (X-ACT) 	1998-2001 	Phase 3 (E-RT-switch-ic)	FULV 	Might have longer OS1 (secondary endpoint)Median OS: NYR vs NYR(HR 0.86, 95% CI 0.74-1.01)Equivalent DFS (primary endpoint)(HR 0.87, 95% CI 0.75-1.00)
Tomita et al. 2019 (JFMC37-0801)	2008-09 to 2009-12 	Phase 3 (C) 	Capecitabine x 12 mo	Might have shorter DFS
1X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 8 cycles
===References===
#X-ACT: Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00009737
##Update: Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. link to original article EuroPMC
#JFMC37-0801: Tomita N, Kunieda K, Maeda A, Hamada C, Yamanaka T, Sato T, Yoshida K, Boku N, Nezu R, Yamaguchi S, Mishima H, Sadahiro S, Muro K, Ishiguro M, Sakamoto J, Saji S, Maehara Y. Phase III randomised trial comparing 6 vs 12-month of capecitabine as adjuvant chemotherapy for patients with stage III colon cancer: final results of the JFMC37-0801 study. Br J Cancer. 2019 Apr;120(7):689-696. Epub 2019 Mar 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==CapeOx==
CapeOx: Capecitabine & Oxaliplatin
CAPOX: CAPecitabine & OXaliplatin
XELOX: XELoda (Capecitabine) & OXaliplatin
===Example orders===
*Example orders for CapeOx (XELOX) in colon cancer
===Regimen variant #1, 3 months===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Yoshino et al. 2019 (ACHIEVE)	2012-08-01 to 2014-06-30	Phase 3 (E-de-esc)	1a. CapeOx x 6 mo1b. mFOLFOX6 x 6 mo	Seems to have non-inferior DFS1 (primary endpoint)DFS60: 75.2% vs 74.2%(HR 0.95, 95% CI 0.77-1.18)
1Reported efficacy is based on the 2022 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
**Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle)
*Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycle for 4 cycles
===Regimen variant #2, 6 months===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Schmoll et al. 2007 (XELOXA) 	2003-04 to 2004-10 	Phase 3 (E-RT-switch-ic)	FULV 	Seems to have longer OS1 (secondary endpoint)OS84: 73% vs 67%(HR 0.83, 95% CI 0.70-0.99)Longer DFS1 (primary endpoint)DFS84: 63% vs 56%(HR 0.80, 95% CI 0.69-0.93)
Yoshino et al. 2019 (ACHIEVE)	2012-08-01 to 2014-06-30	Phase 3 (C) 	1a. CapeOx x 3 mo1b. mFOLFOX6 x 3 mo	Seems to have non-inferior DFS2DFS60: 74.2% vs 75.2%(HR 1.05, 95% CI 0.85-1.30)
1Reported efficacy for XELOXA is based on the 2015 update.
2Reported efficacy for ACHIEVE is based on the 2022 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
**Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle)
*Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycle for 8 cycles
===References===
#XELOXA: Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00069121
##Update: Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011 Apr 10;29(11):1465-71. Epub 2011 Mar 7. link to original article EuroPMC
##Update: Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. link to original article EuroPMC
#IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article EuroPMC NCT01308086
##Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article EuroPMC
##Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article EuroPMC
#ACHIEVE: Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000008543
##Update: Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. link to original article EuroPMC
#TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article EuroPMC NCT00646607
#KCSG CO09-07: Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. link to original article link to PMC article EuroPMC NCT01092481
#CIRCULATE-IDEA: NCT05174169
==FLOX==
FLOX: Fluorouracil, Leucovorin, OXaliplatin
===Example orders===
*Example orders for FLOX in colon cancer
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kuebler et al. 2007 (NSABP C-07)	2000-2002 	Phase 3 (E-esc)	FULV 	Longer DFS (primary endpoint)DFS48: 73.2% vs 67%(HR 0.80, 95% CI 0.69-0.93)
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given third, 1 hour after start of leucovorin
*Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given second
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29, given first
8-week cycle for 3 cycles
===References===
#NSABP C-07: Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00004931
##Update: Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. link to original article link to PMC article EuroPMC
==FOLFOX4==
FOLFOX4: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin 
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
André et al. 2004 (MOSAIC) 	1998-2001 	Phase 3 (E-RT-esc)	FULV 	Seems to have longer OS1 (secondary endpoint)OS120: 71.7% vs 67.1%(HR 0.85, 95% CI 0.73-0.99)Longer DFS (primary endpoint)DFS36: 78.2% vs 72.9%
de Gramont et al. 2012 (AVANT)	2004-2007 	Phase 3 (C) 	1. FOLFOX4 & Bevacizumab 	Did not meet primary endpoint of DFS
de Gramont et al. 2012 (AVANT)	2004-2007 	Phase 3 (C) 	2. XELOX & Bevacizumab 	Did not meet primary endpoint of DFS
Taieb et al. 2014 (PETACC-8) 	2005-2009 	Phase 3 (C) 	FOLFOX4 & Cetuximab 	Did not meet primary endpoint of DFS
Grothey et al. 2018 (IDEA) 	2007-2015 	Phase 3 (C) 	1a. FOLFOX4 x 61b. mFOLFOX6 x 3 mo1c. CapeOx x 3 mo	Inconclusive whether non-inferior DFS36
1Reported efficacy for MOSAIC is based on the 2015 update.
IDEA is a pooled analysis of six phase 3 RCTs.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given second (total dose per cycle: 2000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first, with oxaliplatin on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with leucovorin
14-day cycle for 12 cycles
===References===
#MOSAIC: André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00275210
##Update: André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. link to original article EuroPMC
##Update: André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. link to original article EuroPMC
#AVANT: de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, André T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012 Dec;13(12):1225-33. Epub 2012 Nov 16. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00112918
##Update: André T, Vernerey D, Im SA, Bodoky G, Buzzoni R, Reingold S, Rivera F, McKendrick J, Scheithauer W, Ravit G, Fountzilas G, Yong WP, Isaacs R, Österlund P, Liang JT, Creemers GJ, Rakez M, Van Cutsem E, Cunningham D, Tabernero J, de Gramont A. Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group. Ann Oncol. 2020 Feb;31(2):246-256. Epub 2019 Dec 18. link to original article EuroPMC
#PETACC-8: Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C; PETACC-8 Study Investigators. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Jul;15(8):862-73. Epub 2014 Jun 11. link to original article EuroPMC NCT00265811
#IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article EuroPMC NCT01308086
##Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article EuroPMC
##Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article EuroPMC
#TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article EuroPMC NCT00646607
==mFOLFOX6==
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Example orders===
*Example orders for mFOLFOX 6 in colon cancer
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Allegra et al. 2009 (NSABP C-08) 	2004-2006 	Phase 3 (C)	mFOLFOX6-B 	Did not meet primary endpoint of DFS1DFS36: 75.1% vs 77.9%(HR 1.08, 95% CI 0.93-1.23)
Grothey et al. 2018 (IDEA) 	2007-2015 	Phase 3 (C)	1a. FOLFOX4 x 61b. mFOLFOX6 x 3 mo1c. CapeOx x 3 mo	Inconclusive whether non-inferior DFS36
André et al. 2018 (IDEA France) 	2009-2014 	Phase 3 (C)	mFOLFOX6 x 3 mo 	Seems to have longer DFS
Meyerhardt et al. 2021 (CALGB 80702)	2010-2015 	Phase 3 (C)	mFOLFOX6 & Celecoxib 	Might have shorter DFSDFS36: 73.4% vs 76.3%(HR 1.12, 95% CI 0.97-1.32)
1Reported efficacy for NSABP C-08 is based on the 2013 update.
Note: CALGB 80702 was a 2 x 2 factorial trial, with the other comparison being 3 vs 6 months of mFOLFOX6. This comparison was made as part of the IDEA collaborative and is reported separately.
====Preceding treatment====
*Surgery, within 10 weeks
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 12 cycles
===References===
#NSABP C-08: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Colangelo LH, Lopa SH, Petrelli NJ, Goldberg RM, Atkins JN, Seay TE, Fehrenbacher L, O'Reilly S, Chu L, Azar CA, Wolmark N. Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J Clin Oncol. 2009 Jul 10;27(20):3385-90. Epub 2009 May 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00096278
## Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011 Jan 1;29(1):11-6. Epub 2010 Oct 12. link to original article link to PMC article EuroPMC
## Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Lopa SH, Wolmark N. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol. 2013 Jan 20;31(3):359-64. Epub 2012 Dec 10. link to original article link to PMC article EuroPMC
#IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article EuroPMC NCT01308086
##Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article EuroPMC
##Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article EuroPMC
#IDEA France: André T, Vernerey D, Mineur L, Bennouna J, Desrame J, Faroux R, Fratte S, Hug de Larauze M, Paget-Bailly S, Chibaudel B, Bez J, Dauba J, Louvet C, Lepere C, Dupuis O, Becouarn Y, Mabro M, Egreteau J, Bouche O, Deplanque G, Ychou M, Galais MP, Ghiringhelli F, Dourthe LM, Bachet JB, Khalil A, Bonnetain F, de Gramont A, Taieb J; PRODIGE investigators, GERCOR, Fédération Française de Cancérologie Digestive, UNICANCER. Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer: disease-free survival results from a randomized, open-label, International Duration Evaluation of Adjuvant (IDEA) France, phase III trial. J Clin Oncol. 2018 May 20;36(15):1469-1477. Epub 2018 Apr 5. link to original article EuroPMC NCT00958737
#TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article EuroPMC NCT00646607
#ACHIEVE-2: Yamazaki K, Yamanaka T, Shiozawa M, Manaka D, Kotaka M, Gamoh M, Shiomi A, Makiyama A, Munemoto Y, Rikiyama T, Fukunaga M, Ueki T, Shitara K, Shinkai H, Tanida N, Oki E, Sunami E, Ohtsu A, Maehara Y, Yoshino T. Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial. Ann Oncol. 2021 Jan;32(1):77-84. Epub 2020 Oct 26. link to original article EuroPMC UMIN000013036
#CALGB 80702: Meyerhardt JA, Shi Q, Fuchs CS, Meyer J, Niedzwiecki D, Zemla T, Kumthekar P, Guthrie KA, Couture F, Kuebler P, Bendell JC, Kumar P, Lewis D, Tan B, Bertagnolli M, Grothey A, Hochster HS, Goldberg RM, Venook A, Blanke C, O'Reilly EM, Shields AF. Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1277-1286. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01150045
##Dataset: Project Data Sphere
#KCSG CO09-07: Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. link to original article link to PMC article EuroPMC NCT01092481
==mFOLFOX6 (L-Leucovorin)==
mFOLFOX6: modified L-FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Example orders===
*Example orders for mFOLFOX 6 in colon cancer
===Regimen variant #1, 3 months, 200 mg/m2 L-LCV===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Yoshino et al. 2019 (ACHIEVE)	2012-08-01 to 2014-06-30	Phase 3 (E-de-esc)	1a. CapeOx x 6 mo1b. mFOLFOX6 x 6 mo	Seems to have non-inferior DFS1 (primary endpoint)DFS60: 75.2% vs 74.2%(HR 0.95, 95% CI 0.77-1.18)
1Reported efficacy is based on the 2022 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
*Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 6 cycles
===Regimen variant #2, 6 months, 200 mg/m2 L-LCV===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Yoshino et al. 2019 (ACHIEVE)	2012-08-01 to 2014-06-30	Phase 3 (C)	1a. CapeOx x 3 mo1b. mFOLFOX6 x 3 mo	Seems to have non-inferior DFS1DFS60: 74.2% vs 75.2%(HR 1.05, 95% CI 0.85-1.30)
1Reported efficacy is based on the 2022 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
*Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 12 cycles
===References===
#ACHIEVE: Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000008543
##Update: Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. link to original article EuroPMC
==FULV==
FULV: 5-FU & LeucoVorin
LV5FU2: LeucoVorin & 5-FU for 2 days
===Example orders===
*Example orders for 5-FU & low-dose Leucovorin (Mayo Clinic regimen - LDLV) in colon cancer
*Example orders for 5-FU & high-dose Leucovorin (Roswell Park regimen - HDLV) in colon cancer
===Regimen variant #1, 500/200, 6 out of 8 weeks===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Papadimitriou et al. 2011	1999-2004 	Phase 3 (C)	IFL 	Did not meet primary endpoint of DFS36
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
*Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
8-week cycle for 4 cycles
===Regimen variant #2, 500/500, 6 out of 8 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wolmark et al. 1993 (NSABP C-03) 	1987-1989 	Phase 3 (E-de-esc) 	MOF 	Longer OS
Wolmark et al. 1999 (NSABP C-04) 	1989-07 to 1990-12 	Phase 3 (E-switch-ooc)	1. 5-FU & Levamisole 	Might have longer OS (co-primary endpoint)
Wolmark et al. 1999 (NSABP C-04) 	1989-07 to 1990-12 	Phase 3 (E-switch-ooc)	2. FULV & Levamisole 	Did not meet co-primary endpoints of DFS/OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-esc) 	1. FULV; low-dose 	Did not meet primary endpoint of OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-esc) 	2. FULV & Levamisole; LDLV 	Did not meet primary endpoint of OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-esc) 	3. 5-FU & Levamisole 	Did not meet primary endpoint of OS
Lembersky et al. 2006 (NSABP C-06) 	1997-1999 	Phase 3 (C) 	Tegafur, Uracil, Folinic acid	Did not meet co-primary endpoints of DFS/OS
Saltz et al. 2007 (CALGB 89803) 	1999-2001 	Phase 3 (C) 	IFL 	Did not meet co-primary endpoints of DFS/OS
Kuebler et al. 2007 (NSABP C-07) 	2000-2002 	Phase 3 (C) 	FLOX 	Shorter DFSDFS48: 67% vs 73.2%(HR 1.25, 95% CI 1.08-1.45)
Schmoll et al. 2007 (XELOXA) 	2003-04 to 2004-10 	Phase 3 (C) 	CapeOx 	Seems to have shorter OS1
1Reported efficacy for XELOXA is based on the 2015 update.
Note: this is often called the "Roswell Park regimen" but the original regimen described by Petrelli et al. 1987 & 1989 used a 5-FU dose of 600 mg/m2.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given second, 1 hour after start of leucovorin
*Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for varying durations: 3 cycles (NSABP C-06, NSABP C-07); 4 cycles (CALGB 89803, Intergroup 0089, XELOXA); 6 cycles (NSABP C-03, NSABP C-04)
===Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fountzilas et al. 2000	1989-1997 	Phase 3 (C)	FULV & IFN alfa-2a	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 600 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given second, 1 hour after start of leucovorin
*Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for 4 cycles
===Regimen variant #4, 1850/100 ("Mayo Clinic regimen")===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Popov et al. 2008 (PETACC-1)	Not reported to 1999	Phase 3 (C)	Raltitrexed	Inconclusive whether non-inferior RFS/OS
Note: This was the lower bound of 5-FU dosing in PETACC-1.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 370 mg/m2 IV bolus once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
===Regimen variant #5, 1850/2500 ("NCI schedule")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wolmark et al. 1998 (NSABP C-05)	1991-1994 	Phase 3 (C)	FULV & Interferon alfa	Did not meet co-primary endpoints of DFS/OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 370 mg/m2 IV over 60 minutes once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) 500 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
28-day cycle for 6 cycles
===Regimen variant #6, 2000/400 ("de Gramont regimen"/LV5FU2)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
André et al. 2003 (GERCOR C96.1) 	1996-1999 	Phase 3 (C)	FULV; monthly	Did not meet primary endpoint of DFS
André et al. 2004 (MOSAIC) 	1998-2001 	Phase 3 (C)	FOLFOX4 	Seems to have shorter OS1
Ychou et al. 2009 (FFCD 9802) 	1998-2002 	Phase 3 (C)	IFL 	Did not meet primary endpoint of DFS
Van Cutsem et al. 2009 (PETACC-3)	2000-2002 	Phase 3 (C)	IFL 	Did not meet primary endpoint of DFS
1Reported efficacy for MOSAIC is based on the 2015 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given second (total dose per cycle: 2000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first
14-day cycle for 12 cycles
===Regimen variant #7, 2000/1000===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Francini et al. 1994	1985-1990 	Phase 3 (E-esc)	Observation	Longer OS (secondary endpoint)OS60: 79% vs 65%
====Preceding treatment====
*Surgery, within 3 weeks
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 5
*Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1 to 5
28-day cycle for 12 cycles
===Regimen variant #8, 2125/100 ("Mayo Clinic regimen")===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Twelves et al. 2005 (X-ACT) 	1998-2001 	Phase 3 (C)	Capecitabine 	Might have shorter OS1
Popov et al. 2008 (PETACC-1)	Not reported to 1999	Phase 3 (C)	Raltitrexed 	Inconclusive whether non-inferior RFS/OS
Köhne et al. 2013 (PETACC-2)	1999-2004 	Phase 3 (C)	1. FULV; LV5FU22. FULV; AIO regimen 3. FULV; TTD regimen	Did not meet primary endpoint of OS60
Schmoll et al. 2007 (XELOXA)	2003-04 to 2004-10 	Phase 3 (C)	XELOX 	Seems to have shorter OS2
1X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.
2Reported efficacy for XELOXA is based on the 2015 update.
Note: This was the upper bound of 5-FU dosing in PETACC-1.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
===Regimen variant #9, 2125/100, with cycle elongation ("Mayo Clinic regimen")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Connell et al. 1997 (CALGB 8896) 	1988-02 to 1989-08 	Phase 3 (E-esc) 	Observation 	Seems to have longer OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-de-esc)	1. FULV; high-dose 	Did not meet primary endpoint of OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-de-esc)	2. FULV & Levamisole; LDLV	Did not meet primary endpoint of OS
Haller et al. 2005 (Intergroup 0089)	1988-1992 	Phase 3 (E-de-esc)	3. 5-FU & Levamisole 	Did not meet primary endpoint of OS
Punt et al. 2002 (Study 157-002) 	1995-1999 	Phase 3 (C) 	1. FULV & Edrecolomab 	Did not meet primary endpoint of OS
Punt et al. 2002 (Study 157-002) 	1995-1999 	Phase 3 (C) 	2. Edrecolomab 	Seems to have longer OS
Fields et al. 2009 (Study 157-001) 	1995-1999 	Phase 3 (C) 	FULV & Edrecolomab 	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 3 cycles, then 35-day cycle for 3 cycles
===References===
#NSABP C-03: Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, Jones J, Mamounas EP, Ore L, Petrelli NJ, Spurr CL, Dimitrov N, Romond EH, Sutherland CM, Kardinal CG, DeFusco PA, Jochimsen P. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993 Oct;11(10):1879-87. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article EuroPMC
#Francini G, Petrioli R, Lorenzini L, Mancini S, Armenio S, Tanzini G, Marsili S, Aquino A, Marzocca G, Civitelli S, Mariani L, De Sando D, Bovenga S, Lorenzi M. Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology. 1994 Apr;106(4):899-906. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CALGB 8896: O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997 Jan;15(1):246-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Pooled update: Erlichman C, O'Connell M, Kahn M, Marsoni S, Torri V, Tardio B, Zaniboni A, Pancera G, Martignoni G, Labianca R, Barni A, Seitz JF, Milan C, Bedenne L, Giovannini M, Letreut YP, Skillings J, Shepard L, Zee B, Petrioli R, Francini G; International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol. 1999 May;17(5):1356-63. link to original article EuroPMC
#NSABP C-05: Wolmark N, Bryant J, Smith R, Grem J, Allegra C, Hyams D, Atkins J, Dimitrov N, Oishi R, Prager D, Fehrenbacher L, Romond E, Colangelo L, Fisher B. Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst. 1998 Dec 2;90(23):1810-6. link to original article EuroPMC
##Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article EuroPMC
#NSABP C-04: Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, Bear HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999 Nov;17(11):3553-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00425152
##Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article EuroPMC
#Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Papavramidis S, Bousoulegas A, Basdanis G, Giannoulis E, Dokmetzioglou J, Katsohis C, Nenopoulou E, Karvounis N, Briassoulis E, Aravantinos G, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Oncology. 2000 Apr;58(3):227-36. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Study 157-002: Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002 Aug 31;360(9334):671-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#GERCOR C96.1: Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, Colbert N, Boaziz C, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Buyse M, de Gramont A. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003 Aug 1;21(15):2896-903. link to original article EuroPMC
##Update: André T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O, Achille E, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Lledo G, Raoul Y, Debrix I, Buyse M, de Gramont A. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol. 2007 Aug 20;25(24):3732-8. link to original article EuroPMC
#MOSAIC: André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00275210
##Update: André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. link to original article EuroPMC
##Update: André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. link to original article EuroPMC
#X-ACT: Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00009737
##Update: Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. link to original article EuroPMC
#Intergroup 0089: Haller DG, Catalano PJ, Macdonald JS, O'Rourke MA, Frontiera MS, Jackson DV, Mayer RJ. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005 Dec 1;23(34):8671-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#NSABP C-06: Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006 May 1;24(13):2059-64. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00378716
#XELOXA: Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00069121
##Update: Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011 Apr 10;29(11):1465-71. Epub 2011 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. link to original article EuroPMC
#NSABP C-07: Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00004931
##Update: Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. link to original article link to PMC article EuroPMC
#CALGB 89803: Saltz LB, Niedzwiecki D, Hollis D, Goldberg RM, Hantel A, Thomas JP, Fields AL, Mayer RJ. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007 Aug 10;25(23):3456-61. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003835
#PETACC-1: Popov I, Carrato A, Sobrero A, Vincent M, Kerr D, Labianca R, Raffaele Bianco A, El-Serafi M, Bedenne L, Paillot B, Mini E, Sanches E, Welch J, Collette L, Praet M, Wils J. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1). Eur J Cancer. 2008 Oct;44(15):2204-11. Epub 2008 Aug 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#FFCD 9802: Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, Viret F, Becouarn Y, Bouché O, Gamelin E, Ducreux M, Conroy T, Seitz JF, Bedenne L, Kramar A. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol. 2009 Apr;20(4):674-80. Epub 2009 Jan 29. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00005979
#Study 157-001: Fields AL, Keller A, Schwartzberg L, Bernard S, Kardinal C, Cohen A, Schulz J, Eisenberg P, Forster J, Wissel P. Adjuvant therapy with the monoclonal antibody edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer. J Clin Oncol. 2009 Apr 20;27(12):1941-7. Epub 2009 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#PETACC-3: Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, André T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. Epub 2009 May 18. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00026273
#Papadimitriou CA, Papakostas P, Karina M, Malettou L, Dimopoulos MA, Pentheroudakis G, Samantas E, Bamias A, Miliaras D, Basdanis G, Xiros N, Klouvas G, Bafaloukos D, Kafiri G, Papaspirou I, Pectasides D, Karanikiotis C, Economopoulos T, Efstratiou I, Korantzis I, Pisanidis N, Makatsoris T, Matsiakou F, Aravantinos G, Kalofonos HP, Fountzilas G; Hellenic Cooperative Oncology Group. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study. BMC Med. 2011 Jan 31;9:10. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC ACTRN12610000148077
#PETACC-2: Köhne CH, Bedenne L, Carrato A, Bouché O, Popov I, Gaspà L, Valladares M, Rougier P, Gog C, Reichardt P, Wils J, Pignatti F, Biertz F; EORTC; FFCD; GETTD. A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: the Pan-European Trial in Adjuvant Colon Cancer 2 study. Eur J Cancer. 2013 May;49(8):1868-75. Epub 2013 Apr 6. link to original article EuroPMC NCT00004150
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Yoshida et al. 2014 (ACTS-CC)	2008-04 to 2009-06 	Phase 3 (E-switch-ic)	UFT + LV 	Non-inferior DFS36 (primary endpoint)DFS36: 75.5% vs 72.5%(HR 0.85, 95% CI 0.70-1.03)
====Preceding treatment====
*Surgery
====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 between 1.25 m2 and 1.50 m2: 50 mg PO twice per day on days 1 to 28
**BSA greater than 1.50 m2: 60 mg PO twice per day on days 1 to 28
42-day cycle for 4 cycles
===References===
#ACTS-CC: Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00660894
==SOX==
SOX: S-1, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sunami et al. 2019 (ACTS-CC 02)	2010-2014 	Phase 3 (E-esc)	Tegafur, Uracil, Folinic Acid	Did not meet primary endpoint of DFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Tegafur, gimeracil, oteracil (S-1) 40 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) 100 mg/m2 IV once on day 1
21-day cycle for 8 cycles
===References===
#ACTS-CC 02: Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC JapicCTI-101073
##Update: Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. link to original article link to PMC article EuroPMC
==Tegafur, Uracil, Folinic acid==
UFT + LV: UFT (Tegafur and uracil) & LeucoVorin (Folinic acid)
===Regimen variant #1, 300/75===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sadahiro et al. 2015 (JFMC33-0502)	2005-2007 	Phase 3 (C)	UFT + LV; weekly x 18 mo	Did not meet primary endpoint of DFS
Yoshida et al. 2014 (ACTS-CC) 	2008-04 to 2009-06 	Phase 3 (C)	S-1 	Non-inferior DFS36DFS36: 72.5% vs 75.5%(HR 1.18, 95% CI 0.97-1.43)
Sunami et al. 2019 (ACTS-CC 02) 	2010-2014 	Phase 3 (C)	SOX 	Did not meet primary endpoint of DFS
Note: In ACTS-CC, this dosing was used for patients with BSA less than 1.17 m2.
====Chemotherapy====
*Tegafur and uracil (UFT) 100 mg/m2 PO every 8 hours on days 1 to 28
*Leucovorin (Folinic acid) 25 mg PO every 8 hours on days 1 to 28
35-day cycle for 5 cycles
===Regimen variant #2, 300/90===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Lembersky et al. 2006 (NSABP C-06)	1997-1999 	Phase 3 (E-switch-ic)	FULV 	Did not meet co-primary endpoints of DFS/OS
====Preceding treatment====
*A potentially curative resection of stage II or stage III colon cancer
====Chemotherapy====
*Tegafur and uracil (UFT) 100 mg/m2 PO every 8 hours on days 1 to 28
*Leucovorin (Folinic acid) 30 mg PO every 8 hours on days 1 to 28
*No food for 1 hour before and after each dose of medication.
35-day cycle for 5 cycles
===References===
#NSABP C-06: Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006 May 1;24(13):2059-64. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00378716
#ACTS-CC: Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00660894
#JFMC33-0502: Sadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, Kakeji Y, Baba H, Sato S, Koda K, Yamaguchi Y, Morita T, Matsuoka J, Usuki H, Hamada C, Kodaira S. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol. 2015 Nov;26(11):2274-80. Epub 2015 Sep 7. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC UMIN C000000245
#ACTS-CC 02: Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC JapicCTI-101073
##Update: Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. link to original article link to PMC article EuroPMC
=Advanced or metastatic disease=
See the colorectal cancer page for colorectal cancer regimens.
Category:Colon cancer regimens
Category:Disease-specific pages
Category:Colorectal cancers