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	Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA LinkedIn

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.

10 regimens on this page 20 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

2022: Baxter et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update PubMed
2019: Lieu et al. Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline PubMed

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 PubMed
2020: Argilés et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
- 2009: van Cutsem & Oliveira. Primary colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2008: van Cutsem & Oliveira. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2007: van Cutsem. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2005: van Cutsem & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer PubMed
2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

NCCN

NCCN Guidelines - Colon Cancer
2021: Benson et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. PubMed
2017: Benson et al. Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
2014: Benson et al. Colon Cancer, Version 3.2014 PubMed
2013: Benson et al. Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines. PubMed
2011: Benson et al. Colon cancer. PubMed
2009: Engstrom et al. NCCN Clinical Practice Guidelines in Oncology: colon cancer. PubMed
2007: Engstrom et al. Colon cancer. PubMed
2005: Engstrom et al. Colon cancer clinical practice guidelines in oncology. PubMed
2003: Engstrom et al. Colon cancer. Clinical practice guidelines in oncology. link to PMC article PubMed

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 superior 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 PubMed 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 superior 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 inferior 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 PubMed NCT00009737
1. 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 PubMed
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 PubMed

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 mo 1b. 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 superior OS¹ (secondary endpoint) OS84: 73% vs 67% (HR 0.83, 95% CI 0.70-0.99) Superior 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 mo 1b. mFOLFOX6 x 3 mo	Seems to have non-inferior DFS

¹Reported efficacy for XELOXA is based on the 2015 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 PubMed NCT00069121
1. 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 PubMed
2. 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 PubMed
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 PubMed NCT01308086
1. 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 PubMed
2. 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 PubMed
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 PubMed UMIN000008543
1. 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 PubMed
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 PubMed 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 PubMed 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	Superior 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 PubMed NCT00004931
1. 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 PubMed

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 superior OS¹ (secondary endpoint) OS120: 71.7% vs 67.1% (HR 0.85, 95% CI 0.73-0.99) Superior 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 6 1b. mFOLFOX6 x 3 mo 1c. 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 PubMed NCT00275210
1. 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 PubMed
2. 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 PubMed
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 PubMed NCT00112918
1. 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 PubMed
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 PubMed 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 PubMed NCT01308086
1. 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 PubMed
2. 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 PubMed
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 PubMed 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 DFS
Grothey et al. 2018 (IDEA)	2007-2015	Phase 3 (C)	1a. FOLFOX4 x 6 1b. mFOLFOX6 x 3 mo 1c. 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 superior DFS
Meyerhardt et al. 2021 (CALGB 80702)	2010-2015	Phase 3 (C)	mFOLFOX6 & Celecoxib	Did not meet primary endpoint of DFS

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 PubMed NCT00096278
1. 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 PubMed
2. 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 PubMed
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 PubMed NCT01308086
1. 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 PubMed
2. 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 PubMed
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 PubMed 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 PubMed 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 PubMed 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 PubMed NCT01150045
1. 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 PubMed 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 mo 1b. 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 mo 1b. mFOLFOX6 x 3 mo	Seems to have non-inferior DFS

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 PubMed UMIN000008543
1. 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 PubMed

FULV

FULV: 5-FU & LeucoVorin
LV5FU2: LeucoVorin & 5-FU for 2 days

Example orders

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	Superior OS
Wolmark et al. 1999 (NSABP C-04)	1989-07 to 1990-12	Phase 3 (E-switch-ooc)	1. 5-FU & Levamisole	Might have superior 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
			2. FULV & Levamisole; LDLV	Did not meet primary endpoint of OS
			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	Inferior DFS
Schmoll et al. 2007 (XELOXA)	2003-04 to 2004-10	Phase 3 (C)	CapeOx	Seems to have inferior 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-07); 3 to 6 cycles

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-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 inferior 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	Superior 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 inferior OS¹
Popov et al. 2008 (PETACC-1)	Not reported-1999	Phase 3 (C)	Raltitrexed	Inconclusive whether non-inferior RFS/OS
Köhne et al. 2013 (PETACC-2)	1999-2004	Phase 3 (C)	1. FULV; LV5FU2 2. 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 inferior 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 superior 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
			2. FULV & Levamisole; LDLV	Did not meet primary endpoint of OS
			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 superior 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 PubMed
1. 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 PubMed
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 PubMed
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 PubMed
1. 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 PubMed
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 PubMed
1. 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 PubMed
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 PubMed NCT00425152
1. 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 PubMed
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 PubMed
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 PubMed
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 PubMed
1. 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 PubMed
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 PubMed NCT00275210
1. 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 PubMed
2. 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 PubMed
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 PubMed NCT00009737
1. 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 PubMed
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 PubMed
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 PubMed 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 PubMed NCT00069121
1. 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 PubMed
2. 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 PubMed
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 PubMed NCT00004931
1. 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 PubMed
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 PubMed 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 PubMed
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 PubMed 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 PubMed
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 PubMed 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 PubMed 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 PubMed 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 PubMed 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 PubMed JapicCTI-101073
1. 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 PubMed

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 DFS36
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 PubMed 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 PubMed 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 PubMed 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 PubMed JapicCTI-101073
1. 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 PubMed

Advanced or metastatic disease

See the colorectal cancer page for colorectal cancer regimens.

@@ Line 1: / Line 1: @@
-{| class="wikitable" style="text-align:center; width:100%;"
+<span id="BackToTop"></span>
-! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Page editor'''
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''
+[[#top|Back to Top]]
-|-
+</div>
-| style="background-color:#F0F0F0; width:15%" |[[File:RyanNguyen.jpg|frameless|upright=0.3|center]]
+{{#lst:Editorial board transclusions|gi}}
-| style="width:35%" |<big>[[User:Ryannguyen|Ryan Nguyen, DO]]<br>University of Illinois at Chicago<br>Chicago, IL</big><br>[https://www.linkedin.com/in/ryan-nguyen-0b12a432/ LinkedIn]
-| style="background-color:#F0F0F0; width:15%" |[[File:nkv.jpg|frameless|upright=0.3|center]]
-| style="width:35%" |<big>[[User:Neetavenepalli|Neeta K. Venepalli, MD, MBA]]<br>University of Illinois at Chicago<br>Chicago, IL</big>
-|-
-|}
 ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Colon_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Colon cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
-<br><big>Note: the page has adjuvant and perioperative regimens specific to colon cancer as well as systemic regimens for the more general category of colorectal cancer.
+<br>'''Note: This page has recently been reorganized, with regimens intended more generically for colorectal cancer being moved to a [[Colorectal_cancer|dedicated page]]. Now, this page has adjuvant regimens specific to colon cancer. Please see the [[Rectal_cancer|'''rectal cancer page''']] for (neo-)adjuvant regimens specific to rectal cancer.
+*See the [[Colon_cancer,_RAS_wild-type|'''RAS wild-type page''']] for biomarker-specific adjuvant regimens.
-*See the [[Rectal_cancer|'''rectal cancer page''']] for regimens specific to rectal cancer.
-*See the [[Colon cancer, BRAF-mutated|'''BRAF-mutated page''']] for biomarker-specific regimens.
-*See the [[Colon cancer, HER2-positive|'''HER2+ page''']] for biomarker-specific regimens.
-*See the [[Colon_cancer,_MSI-H_or_dMMR|'''MSI-H/dMMR page''']] for biomarker-specific regimens.
-*See the [[Colon_cancer,_RAS_wild-type|'''RAS wild-type page''']] for biomarker-specific regimens.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 24: / Line 13: @@
 |}
 {{TOC limit|limit=3}}
 =Guidelines=
-==[http://www.asco.org/ ASCO]==
+'''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.'''
+==[https://www.asco.org/ ASCO]==
-*'''2019:''' Lieu et al. [https://doi.org/10.1200/JCO.19.00281 Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline]
+*'''2022:''' Baxter et al. [https://doi.org/10.1200/jco.21.02538 Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/34936379/ PubMed]
+*'''2019:''' Lieu et al. [https://doi.org/10.1200/JCO.19.00281 Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/30986117/ PubMed]
-==[http://www.esmo.org/ ESMO]==
+==[https://www.esmo.org/ ESMO]==
-*'''2021:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2021.08.1752 Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer]
+*'''2021:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2021.08.1752 Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer] [https://pubmed.ncbi.nlm.nih.gov/34411693 PubMed]
-*'''2020:''' Argilés et al. [https://doi.org/10.1016/j.annonc.2020.06.022 Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+*'''2020:''' Argilés et al. [https://doi.org/10.1016/j.annonc.2020.06.022 Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/32702383 PubMed]
-*'''2019:''' Stjepanovic et al. [https://doi.org/10.1093/annonc/mdz233 Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+**'''2013:''' Labianca et al. [https://doi.org/10.1093/annonc/mdt354 Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664 PubMed]
-*'''2016:''' Van Cutsem et al. [https://doi.org/10.1093/annonc/mdw235 ESMO consensus guidelines for the management of patients with metastatic colorectal cancer]
+**'''2009:''' van Cutsem & Oliveira. [https://doi.org/10.1093/annonc/mdp126 Primary colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454461/ PubMed]
+**'''2008:''' van Cutsem & Oliveira. [https://doi.org/10.1093/annonc/mdn077 Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456758/ PubMed]
-===Older===
+**'''2007:''' van Cutsem. [https://doi.org/10.1093/annonc/mdm021 Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491030/ PubMed]
+**'''2005:''' van Cutsem & Kataja. [https://doi.org/10.1093/annonc/mdi808 ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer] [https://pubmed.ncbi.nlm.nih.gov/15888737/ PubMed]
-*'''2013:''' Labianca et al. [https://doi.org/10.1093/annonc/mdt354 Early Colon Cancer: ESMO Clinical Practice Guidelines]
+**'''2001:''' [https://doi.org/10.1023/a:1017492920758 ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer] [https://pubmed.ncbi.nlm.nih.gov/11583182/ PubMed]
-*'''2013:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdt209 Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines]
+*'''2019:''' Stjepanovic et al. [https://doi.org/10.1093/annonc/mdz233 Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/31378807 PubMed]
-==[http://www.jsccr.jp/en/index.html Japanese Society for Cancer of the Colon and Rectum (JSCCR)]==
-*'''2016:''' Watanabe et al. [https://doi.org/10.1007/s10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5809573/ link to PMC article]
-==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer]
-==[http://www.siog.org/ SIOG]==
-*'''2014:''' Papamichael et al. [https://doi.org/10.1093/annonc/mdu253 Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013]
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428 NCCN Guidelines - Colon Cancer]
+*'''2021:''' Benson et al. [https://doi.org/10.6004/Jnccn.2021.0012 Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/33724754/ PubMed]
+*'''2017:''' Benson et al. [https://doi.org/10.6004/jnccn.2017.0036 Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/28275037/ PubMed]
+*'''2014:''' Benson et al. [https://doi.org/10.6004/jnccn.2014.0099 Colon Cancer, Version 3.2014] [https://pubmed.ncbi.nlm.nih.gov/24994923/ PubMed]
+*'''2013:''' Benson et al. [https://doi.org/10.6004/Jnccn.2013.0069 Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23667203/ PubMed]
+*'''2011:''' Benson et al. [https://doi.org/10.6004/Jnccn.2011.0104 Colon cancer.] [https://pubmed.ncbi.nlm.nih.gov/22056656/ PubMed]
+*'''2009:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2009.0056 NCCN Clinical Practice Guidelines in Oncology: colon cancer.] [https://pubmed.ncbi.nlm.nih.gov/19755046/ PubMed]
+*'''2007:''' Engstrom et al. Colon cancer. [https://pubmed.ncbi.nlm.nih.gov/17977501/ PubMed]
+*'''2005:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2005.0024 Colon cancer clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/16038639/ PubMed]
+*'''2003:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2003.0006 Colon cancer. Clinical practice guidelines in oncology.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613831/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19764149/ PubMed]
-=Adjuvant therapy=
+=Perioperative therapy=
-==Capecitabine monotherapy {{#subobject:7b50df|Regimen=1}}==
+==mFOLFOX6 (L-Leucovorin) {{#subobject:8uy6d7|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-|-
+<div class="toccolours" style="background-color:#c8a2c8">
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:ed4e3f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022855/ Morton et al. 2023 (FOxTROT)]
-|1998-2001
+|2008-05-15 to 2016-12-23
-| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#FULV|FULV]]
+|[[#mFOLFOX6_.28L-Leucovorin.29_2|mFOLFOX6]]; adjuvant
-| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> <br>(HR 0.86, 95% CI 0.74-1.01)
+| style="background-color:#91cf60" |Seems to have superior rate of residual or recurrent disease within 2 years (primary endpoint)<br>Rate: 16.9% vs 21.5%<br>(RR 0.72, 95% CI 0.54-0.98)
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30172-3/fulltext Kerr et al. 2016 (QUASAR 2)]
+|}
-|2005-2010
+''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.''
-| style="background-color:#1a9851" |Phase 3 (C)
+<div class="toccolours" style="background-color:#eeeeee">
-|Capecitabine & Bevacizumab
+===Neoadjuvant {{#subobject:30juz2|Variant=1}}===
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
+<div class="toccolours" style="background-color:#b3e2cd">
-|-
+====Chemotherapy====
-|[https://www.nature.com/articles/s41416-019-0410-0 Tomita et al. 2019 (JFMC37-0801)]
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-|2008-2009
+*[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+'''14-day cycle for 3 cycles, followed by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Definitive===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Local therapy====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Adjuvant===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+'''14-day cycle for 9 cycles'''
+</div></div></div>
+===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. [https://doi.org/10.1200/JCO.22.00046 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022855/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36657089/ PubMed] [https://clinicaltrials.gov/study/NCT00647530 NCT00647530]
+=Adjuvant therapy=
+==Capecitabine monotherapy {{#subobject:7b50df|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ed4e3f|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)]
+|1998-2001
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+|[[#FULV|FULV]]
+| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.86, 95% CI 0.74-1.01)<br><br>Equivalent DFS (primary endpoint)<br>(HR 0.87, 95% CI 0.75-1.00)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6461756/ Tomita et al. 2019 (JFMC37-0801)]
+|2008-09 to 2009-12
 | style="background-color:#1a9851" |Phase 3 (C)
 |[[#Capecitabine_monotherapy|Capecitabine]] x 12 mo
 | style="background-color:#fee08b" |Might have inferior DFS
-|-
-|[https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30297-2/fulltext Hamaguchi et al. 2017 (JCOG0910)]
-|2010-2013
-| style="background-color:#1a9851" |Phase 3 (C)
-|S-1
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS
 |-
 |}
 ''<sup>1</sup>X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycle for 8 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1056/NEJMoa043116 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15987918/ PubMed] [https://clinicaltrials.gov/study/NCT00009737 NCT00009737]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa043116 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15987918 PubMed] 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. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539/ PubMed]
-##'''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. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539 PubMed]
+#'''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. [https://doi.org/10.1038/s41416-019-0410-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6461756/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30833647/ PubMed]
-#'''QUASAR 2:''' Kerr RS, Love S, Segelov E, Johnstone E, Falcon B, Hewett P, Weaver A, Church D, Scudder C, Pearson S, Julier P, Pezzella F, Tomlinson I, Domingo E, Kerr DJ. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial. Lancet Oncol. 2016 Nov;17(11):1543-1557. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30172-3/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/27660192 PubMed] ISRCTN45133151
-#'''JCOG0910:''' Hamaguchi T, Shimada Y, Mizusawa J, Kinugasa Y, Kanemitsu Y, Ohue M, Fujii S, Takiguchi N, Yatsuoka T, Takii Y, Ojima H, Masuko H, Kubo Y, Mishima H, Yamaguchi T, Bando H, Sato T, Kato T, Nakamura K, Fukuda H, Moriya Y. Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):47-56. Epub 2017 Oct 24. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30297-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/29079411 PubMed] UMIN000003272
-#'''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. [https://www.nature.com/articles/s41416-019-0410-0 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/30833647 PubMed]
 ==CapeOx {{#subobject:cf9acc|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 CapeOx: '''<u>Cape</u>'''citabine & '''<u>Ox</u>'''aliplatin
 <br>CAPOX: '''<u>CAP</u>'''ecitabine & '''<u>OX</u>'''aliplatin
 <br>XELOX: '''<u>XEL</u>'''oda (Capecitabine) & '''<u>OX</u>'''aliplatin
 ===Example orders===
 *[[Example orders for CapeOx (XELOX) in colon cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 3 months {{#subobject:205ad6|Variant=1}}===
+===Regimen variant #1, 3 months {{#subobject:jgui19a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
-|2008-2013
+|2012-08-01 to 2014-06-30
 | style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#CapeOx|CapeOx]] x 6 mo
+|1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
+| style="background-color:#eeee01" |Seems to have non-inferior DFS<sup>1</sup> (primary endpoint)<br>DFS60: 75.2% vs 74.2%<br>(HR 0.95, 95% CI 0.77-1.18)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2022 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> 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/m<sup>2</sup> IV over 2 hours once on day 1
 '''21-day cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 6 months {{#subobject:1ef938|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 158: / Line 170: @@
 |-
 |[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
-|2003-2004
+|2003-04 to 2004-10
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 |[[#FULV|FULV]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> <br>(HR 0.83, 95% CI 0.70-0.99)
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>OS84: 73% vs 67%<br>(HR 0.83, 95% CI 0.70-0.99)<br><br>Superior DFS<sup>1</sup> (primary endpoint)<br>DFS84: 63% vs 56%<br>(HR 0.80, 95% CI 0.69-0.93)
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445286/ Pectasides et al. 2015]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
-|2005-2008
+|2012-08-01 to 2014-06-30
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237801/ Snoeren et al. 2017 (HEPATICA)]
-|NR
-| style="background-color:#1a9851" |Phase 3 (C)
-|CapeOx & Bevacizumab
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
-|2008-2013
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#CapeOx|CapeOx]] x 3 mo
+|1a. [[#CapeOx|CapeOx]] x 3 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo
 | style="background-color:#eeee01" |Seems to have non-inferior DFS
 |-
 |}
-''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br>
+''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.''
-''Note: HEPATICA enrolled patients with resected colorectal liver metastases.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> 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/m<sup>2</sup> IV over 2 hours once on day 1
 '''21-day cycle for 8 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17194911/ PubMed] [https://clinicaltrials.gov/study/NCT00069121 NCT00069121]
-#'''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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17194911 PubMed] 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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21383294/ PubMed]
-##'''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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21383294 PubMed]
+##'''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. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362/ PubMed]
-##'''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. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362 PubMed]
+#'''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. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 NCT01308086]
-#Pectasides D, Karavasilis V, Papaxoinis G, Gourgioti G, Makatsoris T, Raptou G, Vrettou E, Sgouros J, Samantas E, Basdanis G, Papakostas P, Bafaloukos D, Kotoula V, Kalofonos HP, Scopa CD, Pentheroudakis G, Fountzilas G. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015 May 10;15:384. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1406-7 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445286/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25956750 PubMed]
+##'''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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed]
-#'''HEPATICA:''' Snoeren N, van Hillegersberg R, Schouten SB, Bergman AM, van Werkhoven E, Dalesio O, Tollenaar RA, Verheul HM, van der Sijp J, Borel Rinkes IH, Voest EE; Hepatica study group. Randomized phase III study to assess efficacy and safety of adjuvant CAPOX with or without bevacizumab in patients after resection of colorectal liver metastases: HEPATICA study. Neoplasia. 2017 Feb;19(2):93-99. Epub 2017 Jan 12. [https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1476558616301701 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237801/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28088688 PubMed]
+##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1713709 link to original article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/29590544 PubMed] NCT01308086
+#'''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. [https://doi.org/10.1001/jamaoncol.2019.2572 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31513248/ PubMed] UMIN000008543
-##'''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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203 PubMed]
+##'''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. [https://doi.org/10.1200/jco.21.02628 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35512259/ PubMed]
-##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33271092 PubMed]
+#'''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. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 NCT00646607]
-#'''SCOT:''' Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Allan K, McQueen J, Scudder C, Boyd KA, Briggs A, Waterston A, Medley L, Wilson C, Ellis R, Essapen S, Dhadda AS, Harrison M, Falk S, Raouf S, Rees C, Olesen RK, Propper D, Bridgewater J, Azzabi A, Farrugia D, Webb A, Cunningham D, Hickish T, Weaver A, Gollins S, Wasan HS, Paul J. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2018 Apr;19(4):562-578. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29611518 PubMed] NCT00749450
+#'''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. [https://doi.org/10.1200/jco.21.02962 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9671755/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35772045/ PubMed] [https://clinicaltrials.gov/study/NCT01092481 NCT01092481]
+#'''CIRCULATE-IDEA:''' [https://clinicaltrials.gov/study/NCT05174169 NCT05174169]
 ==FLOX {{#subobject:617cc1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 FLOX: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>OX</u>'''aliplatin
 ===Example orders===
 *[[Example orders for FLOX in colon cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c80e20|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 231: / Line 225: @@
 | style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#FULV|FULV]]
-| style="background-color:#1a9850" |Superior DFS
+| style="background-color:#1a9850" |Superior DFS (primary endpoint)<br>DFS48: 73.2% vs 67%<br>(HR 0.80, 95% CI 0.69-0.93)
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given third, 1 hour after start of leucovorin'''
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second'''
+*[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second'''
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, '''given first'''
 '''8-week cycle for 3 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17470851/ PubMed] [https://clinicaltrials.gov/study/NCT00004931 NCT00004931]
-#'''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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17470851 PubMed] 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. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995/ PubMed]
-##'''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. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995 PubMed]
 ==FOLFOX4 {{#subobject:f61339|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+FOLFOX4: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#top|back to top]]
-|}
-FOLFOX4: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 ===Regimen {{#subobject:671bbe|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
+|[https://doi.org/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
 |1998-2001
 | style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[#FULV|FULV]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> <br>(HR 0.85, 95% CI 0.73-0.99)
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>OS120: 71.7% vs 67.1%<br>(HR 0.85, 95% CI 0.73-0.99)<br><br>Superior DFS (primary endpoint)<br>DFS36: 78.2% vs 72.9%
 |-
-| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70509-0/fulltext de Gramont et al. 2012 (AVANT)]
+| rowspan="2" |[https://doi.org/10.1016/S1470-2045(12)70509-0 de Gramont et al. 2012 (AVANT)]
 |rowspan=2|2004-2007
 | rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. FOLFOX4 & Bevacizumab
+|1. [[#FOLFOX4_.26_Bevacizumab_999|FOLFOX4 & Bevacizumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|2. XELOX & Bevacizumab
+|2. [[#CapeOx_.26_Bevacizumab_999|XELOX & Bevacizumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70227-X/fulltext Taieb et al. 2014 (PETACC-8)]
+|[https://doi.org/10.1016/S1470-2045(14)70227-X Taieb et al. 2014 (PETACC-8)]
 |2005-2009
 | style="background-color:#1a9851" |Phase 3 (C)
-|FOLFOX4 & Cetuximab
+|[[#FOLFOX4_.26_Cetuximab_999|FOLFOX4 & Cetuximab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713709 Grothey et al. 2018 (IDEA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ Grothey et al. 2018 (IDEA)]
 |2007-2015
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#FOLFOX4|FOLFOX4]] x 6
+|1a. [[#FOLFOX4|FOLFOX4]] x 6<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo<br>1c. [[#CapeOx|CapeOx]] x 3 mo
 | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
 |-
 |}
-''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2009 update.''<br>
+''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2015 update.''<br>
-''IDEA is a pooled analysis of six phase III RCTs.''
+''IDEA is a pooled analysis of six phase 3 RCTs.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first, with oxaliplatin on day 1'''
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first, with oxaliplatin on day 1'''
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with leucovorin'''
 '''14-day cycle for 12 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1056/NEJMoa032709 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15175436/ PubMed] [https://clinicaltrials.gov/study/NCT00275210 NCT00275210]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa032709 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15175436 PubMed] 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. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431/ PubMed]
-##'''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. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431 PubMed]
+##'''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. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776/ PubMed]
-##'''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. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776 PubMed]
+#'''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. [https://doi.org/10.1016/S1470-2045(12)70509-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23168362/ PubMed] [https://clinicaltrials.gov/study/NCT00112918 NCT00112918]
-#'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70509-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/23168362 PubMed] 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. [https://doi.org/10.1016/j.annonc.2019.12.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31959341/ PubMed]
-##'''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. [https://doi.org/10.1016/j.annonc.2019.12.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31959341 PubMed]
+#'''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. [https://doi.org/10.1016/S1470-2045(14)70227-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/24928083/ PubMed] [https://clinicaltrials.gov/study/NCT00265811 NCT00265811]
-#'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70227-X/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/24928083 PubMed] 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. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 NCT01308086]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1713709 link to original article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/29590544 PubMed] 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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed]
-##'''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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203 PubMed]
+##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed]
-##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33271092 PubMed]
+#'''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. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 NCT00646607]
 ==mFOLFOX6 {{#subobject:32d6c5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-|-
-|[[#top|back to top]]
-|}
-mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 ===Example orders===
 *[[Example orders for mFOLFOX 6 in colon cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 3 months {{#subobject:205ad6|Variant=1}}===
+===Regimen {{#subobject:30juz2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ Allegra et al. 2009 (NSABP C-08)]
-|2008-2013
+|2004-2006
-| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 6 mo
+|[[Colon_cancer_-_historical#mFOLFOX6-B|mFOLFOX6-B]]
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ Grothey et al. 2018 (IDEA)]
+|2007-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#FOLFOX4|FOLFOX4]] x 6<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo<br>1c. [[#CapeOx|CapeOx]] x 3 mo
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
+|-
+|[https://doi.org/10.1200/JCO.2017.76.0355 André et al. 2018 (IDEA France)]
+|2009-2014
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#mFOLFOX6_2|mFOLFOX6]] x 3 mo
+| style="background-color:#91cf60" |Seems to have superior DFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8025124/ Meyerhardt et al. 2021 (CALGB 80702)]
+|2010-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#mFOLFOX6_.26_Celecoxib_999|mFOLFOX6 & Celecoxib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |}
+''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.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
-*[[Folinic acid (Leucovorin)]] 350 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+'''14-day cycle for 12 cycles'''
+</div></div>
+===References===
+<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
+#'''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. [https://doi.org/10.1200/jco.2009.21.9220 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19414665/ PubMed] [https://clinicaltrials.gov/study/NCT00096278 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. [https://doi.org/10.1200/JCO.2010.30.0855 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20940184/ PubMed]
+## '''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. [https://doi.org/10.1200/JCO.2012.44.4711 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233715/ PubMed]
+#'''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. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed]
+##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed]
+#'''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. [https://doi.org/10.1200/JCO.2017.76.0355 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29620995/ PubMed] [https://clinicaltrials.gov/study/NCT00958737 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. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 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. [https://doi.org/10.1016/j.annonc.2020.10.480 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33121997/ PubMed] 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. [https://doi.org/10.1001/jama.2021.2454 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8025124/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33821899/ PubMed] [https://clinicaltrials.gov/study/NCT01150045 NCT01150045]
+##'''Dataset:''' [https://data.projectdatasphere.org/projectdatasphere/html/content/489 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. [https://doi.org/10.1200/jco.21.02962 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9671755/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35772045/ PubMed] [https://clinicaltrials.gov/study/NCT01092481 NCT01092481]
-'''14-day cycle for 6 cycles'''
+==mFOLFOX6 (L-Leucovorin) {{#subobject:32d6d7|Regimen=1}}==
+mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-===Regimen variant #2, 6 months (LCV 200 mg/m<sup>2</sup>) {{#subobject:30b6e7|Variant=1}}===
+===Example orders===
+*[[Example orders for mFOLFOX 6 in colon cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 3 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38ig9a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445286/ Pectasides et al. 2015]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
-|2005-2008
+|2012-08-01 to 2014-06-30
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#CapeOx|CAPOX]]
+|1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+| style="background-color:#eeee01" |Seems to have non-inferior DFS<sup>1</sup> (primary endpoint)<br>DFS60: 75.2% vs 74.2%<br>(HR 0.95, 95% CI 0.77-1.18)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2022 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+'''14-day cycle for 6 cycles'''
-'''14-day cycle for 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 6 months (LCV 350 mg/m<sup>2</sup>) {{#subobject:308ic7|Variant=1}}===
+===Regimen variant #2, 6 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38guh7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
-|2008-2013
+|2012-08-01 to 2014-06-30
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 3 mo
+|1a. [[#CapeOx|CapeOx]] x 3 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo
 | style="background-color:#eeee01" |Seems to have non-inferior DFS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 350 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
 '''14-day cycle for 12 cycles'''
+</div></div>
-===Regimen variant #4, 6 months (LCV 400 mg/m<sup>2</sup>) {{#subobject:30juz2|Variant=1}}===
+===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. [https://doi.org/10.1001/jamaoncol.2019.2572 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31513248/ PubMed] 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. [https://doi.org/10.1200/jco.21.02628 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35512259/ PubMed]
+==FULV {{#subobject:a93a|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin
+<br>LV5FU2: '''<u>L</u>'''euco'''<u>V</u>'''orin & '''<u>5-FU</u>''' for '''<u>2</u>''' 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]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 500/200, 6 out of 8 weeks {{#subobject:2c3f1b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ Allegra et al. 2009 (NSABP C-08)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ Papadimitriou et al. 2011]
-|2004-2006
+|1999-2004
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Colon_cancer_-_historical#mFOLFOX6-B|mFOLFOX6-B]]
+|[[#IFL_999|IFL]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713709 Grothey et al. 2018 (IDEA)]
-|2007-2015
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 3 mo
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
-|-
-|[https://doi.org/10.1200/JCO.2017.76.0355 André et al. 2018 (IDEA France)]
-|2009-2014
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 3 mo
-| style="background-color:#91cf60" |Seems to have superior DFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ Meyerhardt et al. 2021 (CALGB 80702)]
-|2010-2015
-| style="background-color:#1a9851" |Phase 3 (C)
-|mFOLFOX6 & Celecoxib
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |}
-''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.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+'''8-week cycle for 4 cycles'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''14-day cycle for 12 cycles'''
+===Regimen variant #2, 500/500, 6 out of 8 weeks {{#subobject:489be0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===References===
+!style="width: 20%"|Study
-<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-#'''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. [https://doi.org/10.1200/jco.2009.21.9220 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19414665 PubMed] NCT00096278
+!style="width: 20%"|Comparator
-##'''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. [https://doi.org/10.1200/JCO.2010.30.0855 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20940184 PubMed]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-##'''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. [https://doi.org/10.1200/JCO.2012.44.4711 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233715 PubMed]
-#Pectasides D, Karavasilis V, Papaxoinis G, Gourgioti G, Makatsoris T, Raptou G, Vrettou E, Sgouros J, Samantas E, Basdanis G, Papakostas P, Bafaloukos D, Kotoula V, Kalofonos HP, Scopa CD, Pentheroudakis G, Fountzilas G. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015 May 10;15:384. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1406-7 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445286/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25956750 PubMed]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1713709 link to original article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/29590544 PubMed] 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. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203 PubMed]
-##'''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. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33271092 PubMed]
-#'''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. [https://doi.org/10.1200/JCO.2017.76.0355 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29620995 PubMed] NCT00958737
-#'''SCOT:''' Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Allan K, McQueen J, Scudder C, Boyd KA, Briggs A, Waterston A, Medley L, Wilson C, Ellis R, Essapen S, Dhadda AS, Harrison M, Falk S, Raouf S, Rees C, Olesen RK, Propper D, Bridgewater J, Azzabi A, Farrugia D, Webb A, Cunningham D, Hickish T, Weaver A, Gollins S, Wasan HS, Paul J. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2018 Apr;19(4):562-578. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29611518 PubMed] NCT00749450
-#'''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. [https://doi.org/10.1001/jama.2021.2454 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025124 link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33821899/ PubMed] NCT01150045
-==mFOLFOX6 (L-Leucovorin) {{#subobject:32d6c5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1200/JCO.1993.11.10.1879 Wolmark et al. 1993 (NSABP C-03)]
-|}
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-258-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
-===Example orders===
-*[[Example orders for mFOLFOX 6 in colon cancer]]
-===Regimen variant #1, 3 months, 175 mg/m<sup>2</sup> L-LCV {{#subobject:205ad6|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
+|} -->
-|2008-2013
+|1987-1989
 | style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#mFOLFOX6|mFOLFOX6]] x 6 mo
+|[[Colon_cancer_-_historical#MOF|MOF]]
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
+| style="background-color:#1a9850" |Superior OS
+|-
+| rowspan="2" |[https://doi.org/10.1200/JCO.1999.17.11.3553 Wolmark et al. 1999 (NSABP C-04)]
+|rowspan=2|1989-07 to 1990-12
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|1. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
+| style="background-color:#d9ef8b" |Might have superior OS (co-primary endpoint)
 |-
-|}
+|2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]]
-====Preceding treatment====
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
+|-
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+| rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)]
+|rowspan=3|1988-1992
-====Chemotherapy====
+| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#FULV|FULV]]; low-dose
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-*[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+|-
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with L-folinic acid'''
+|2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]]; LDLV
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-'''14-day cycle for 6 cycles'''
-===Regimen variant #2, 3 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38ig9a|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
+|3. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
-|2012-2014
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#mFOLFOX6|mFOLFOX6]] x 6 mo
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
 |-
-|}
+|[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)]
-====Preceding treatment====
+|1997-1999
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+|[[#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic acid]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
-'''14-day cycle for 6 cycles'''
-===Regimen variant #3, 6 months, 175 mg/m<sup>2</sup> L-LCV {{#subobject:372bh7|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext Iveson et al. 2018 (SCOT)]
+|[https://doi.org/10.1200/JCO.2007.11.2144 Saltz et al. 2007 (CALGB 89803)]
-|2008-2013
+|1999-2001
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 3 mo
+|[[#IFL_999|IFL]]
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
 |-
-|}
+|[https://doi.org/10.1200/jco.2006.08.2974 Kuebler et al. 2007 (NSABP C-07)]
-====Preceding treatment====
+|2000-2002
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks
+|[[#FLOX|FLOX]]
+| style="background-color:#d73027" |Inferior DFS
+|-
+|[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
+|2003-04 to 2004-10
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CapeOx|CapeOx]]
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+|-
+|}
+''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br>
+''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/m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> 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/m<sup>2</sup> 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-07); 3 to 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+===Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen") {{#subobject:50ybe0|Variant=1}}===
-*[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
-'''14-day cycle for 12 cycles'''
-===Regimen variant #4, 6 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38guh7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
+|[https://doi.org/10.1159/000012105 Fountzilas et al. 2000]
-|2012-2014
+|1989-1997
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6|mFOLFOX6]] x 3 mo
+|[[#FULV_.26_Interferon_alfa-2a_999|FULV & IFN alfa-2a]]
-| style="background-color:#eeee01" |Seems to have non-inferior DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 hour after start of leucovorin'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
-*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin'''
+'''8-week cycle for 4 cycles'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''14-day cycle for 12 cycles'''
+===Regimen variant #4, 1850/100 ("Mayo Clinic regimen") {{#subobject:4bnc36|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===References===
-#'''SCOT:''' Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Allan K, McQueen J, Scudder C, Boyd KA, Briggs A, Waterston A, Medley L, Wilson C, Ellis R, Essapen S, Dhadda AS, Harrison M, Falk S, Raouf S, Rees C, Olesen RK, Propper D, Bridgewater J, Azzabi A, Farrugia D, Webb A, Cunningham D, Hickish T, Weaver A, Gollins S, Wasan HS, Paul J. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2018 Apr;19(4):562-578. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30093-7/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29611518 PubMed] NCT00749450
-#'''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. Erratum in: JAMA Oncol. 2019 Dec 19. [https://doi.org/10.1001/jamaoncol.2019.2572 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31513248 PubMed] UMIN000008543
-==FULV {{#subobject:a93a|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
-<br>LV5FU2: '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) & '''<u>5-FU</u>''' for '''<u>2</u>''' 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 {{#subobject:2c3f1b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ Papadimitriou et al. 2011]
+|[https://doi.org/10.1016/j.ejca.2008.07.002 Popov et al. 2008 (PETACC-1)]
-|1999-2004
+|Not reported-1999
 | style="background-color:#1a9851" |Phase 3 (C)
-|IFL
+|[[#Raltitrexed_monotherapy_999|Raltitrexed]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS/OS
 |-
 |}
+''Note: This was the lower bound of 5-FU dosing in PETACC-1.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second'''
-*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
+*[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first'''
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
+'''28-day cycle for 6 cycles'''
+</div></div><br>
-'''8-week cycle for 4 cycles'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 1850/2500 ("NCI schedule") {{#subobject:7cc2b9|Variant=1}}===
-===Regimen variant #2, 500/500, 6 out of 8 weeks {{#subobject:489be0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1993.11.10.1879 Wolmark et al. 1993 (NSABP C-03)]
+|[https://doi.org/10.1093/jnci/90.23.1810 Wolmark et al. 1998 (NSABP C-05)]
-|1987-1989
+|1991-1994
-| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Colon_cancer_-_historical#MOF|MOF]]
+|[[#FULV_.26_Interferon_alfa_999|FULV & Interferon alfa]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
 |-
-| rowspan="2" |[https://doi.org/10.1200/JCO.1999.17.11.3553 Wolmark et al. 1999 (NSABP C-04)]
+|}
-|rowspan=2|1989-1990
+<div class="toccolours" style="background-color:#cbd5e8">
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+====Preceding treatment====
-|1. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-| style="background-color:#d9ef8b" |Might have superior OS
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given second'''
+*[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first'''
+'''28-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #6, 2000/400 ("de Gramont regimen"/LV5FU2) {{#subobject:685f89|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|2. FULV & Levamisole
+|[https://doi.org/10.1200/JCO.2003.10.065 André et al. 2003 (GERCOR C96.1)]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
+|1996-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FULV|FULV]]; monthly
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-| rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)]
+|[https://doi.org/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
-|rowspan=3|1988-1992
+|1998-2001
-| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#FULV|FULV]]; low-dose
+|[[#FOLFOX4|FOLFOX4]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
-|2. LDLV & Levamisole
+|[https://doi.org/10.1093/annonc/mdn680 Ychou et al. 2009 (FFCD 9802)]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|1998-2002
-|-
-|3. 5-FU & Levamisole
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)]
-|1997-1999
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic acid]]
+|[[#IFL_999|IFL]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|[https://doi.org/10.1200/JCO.2007.11.2144 Saltz et al. 2007 (CALGB 89803)]
+|[https://doi.org/10.1200/JCO.2008.21.6663 Van Cutsem et al. 2009 (PETACC-3)]
-|1999-2001
-| style="background-color:#1a9851" |Phase 3 (C)
-|IFL
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
-|-
-|[https://doi.org/10.1200/jco.2006.08.2974 Kuebler et al. 2007 (NSABP C-07)]
 |2000-2002
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#FLOX|FLOX]]
+|[[#IFL_999|IFL]]
-| style="background-color:#d73027" |Inferior DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
-|2003-2004
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CapeOx|CapeOx]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
 |}
-''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br>
+''<sup>1</sup>Reported efficacy for MOSAIC 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/m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
-*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 hour after start of leucovorin'''
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first'''
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
+'''14-day cycle for 12 cycles'''
+</div></div><br>
-'''8-week cycle for 3 to 6 cycles'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #7, 2000/1000 {{#subobject:6igjc9|Variant=1}}===
-===Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen") {{#subobject:50ybe0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.karger.com/Article/Abstract/12105 Fountzilas et al. 2000]
+|[https://doi.org/10.1016/0016-5085(94)90748-x Francini et al. 1994]
-|1989-1997
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase 3 (C)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-259-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
-|FULV & IFN alfa-2a
+|-
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|} -->
+|1985-1990
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Colon_cancer_-_null_regimens#Observation_2|Observation]]
+| style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>OS60: 79% vs 65%
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]], within 3 weeks
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 hour after start of leucovorin'''
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
+'''28-day cycle for 12 cycles'''
+</div></div><br>
-'''8-week cycle for 4 cycles'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #8, 2125/100 ("Mayo Clinic regimen") {{#subobject:4bd336|Variant=1}}===
-===Regimen variant #4, 1850/2500 ("NCI schedule") {{#subobject:7cc2b9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://academic.oup.com/jnci/article/90/23/1810/2520545 Wolmark et al. 1998 (NSABP C-05)]
+||[https://doi.org/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)]
-|1991-1994
+|1998-2001
 | style="background-color:#1a9851" |Phase 3 (C)
-|FULV & Interferon alfa
+|[[#Capecitabine_monotherapy|Capecitabine]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
+| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 |-
-|}
+|[https://doi.org/10.1016/j.ejca.2008.07.002 Popov et al. 2008 (PETACC-1)]
+|Not reported-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Raltitrexed_monotherapy_999|Raltitrexed]]
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS/OS
+|-
+|[https://doi.org/10.1016/j.ejca.2013.01.030 Köhne et al. 2013 (PETACC-2)]
+|1999-2004
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#FULV|FULV]]; LV5FU2<br>2. [[#FULV|FULV]]; AIO regimen<br> 3. [[#FULV|FULV]]; TTD regimen
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60
+|-
+|[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
+|2003-04 to 2004-10
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CapeOx|XELOX]]
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup>
+|-
+|}
+''<sup>1</sup>X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.''<br>
+''<sup>2</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br>
+''Note: This was the upper bound of 5-FU dosing in PETACC-1.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second'''
-*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given second'''
+*[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first'''
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first'''
 '''28-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 2000/400 ("de Gramont regimen"/LV5FU2) {{#subobject:685f89|Variant=1}}===
+===Regimen variant #9, 2125/100, with cycle elongation ("Mayo Clinic regimen") {{#subobject:e24014|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2003.10.065 André et al. 2003 (GERCOR C96.1)]
+|[https://doi.org/10.1200/jco.1997.15.1.246 O'Connell et al. 1997 (CALGB 8896)]
-|1996-1999
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase 3 (C)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-260-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
-|[[#FULV|FULV]]; monthly
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
+|} -->
-|1998-2001
+|1988-02 to 1989-08
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#FOLFOX4|FOLFOX4]]
+|[[Colon_cancer_-_null_regimens#Observation|Observation]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+| rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)]
+|rowspan=3|1988-1992
+| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|1. [[#FULV|FULV]]; high-dose
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]]; LDLV
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|3. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+| rowspan="2" |[https://doi.org/10.1016/s0140-6736(02)09836-7 Punt et al. 2002 (Study 157-002)]
+|rowspan=2|1995-1999
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#FULV_.26_Edrecolomab_999|FULV & Edrecolomab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1093/annonc/mdn680 Ychou et al. 2009 (FFCD 9802)]
+|2. [[Colon_cancer_-_historical#Edrecolomab_monotherapy|Edrecolomab]]
-|1998-2002
+| style="background-color:#91cf60" |Seems to have superior OS
-| style="background-color:#1a9851" |Phase 3 (C)
-|IFL
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-|[https://doi.org/10.1200/JCO.2008.21.6663 Van Cutsem et al. 2009 (PETACC-3)]
+|[https://doi.org/10.1200/JCO.2008.18.5710 Fields et al. 2009 (Study 157-001)]
-|2000-2002
+|1995-1999
 | style="background-color:#1a9851" |Phase 3 (C)
-|IFL
+|[[#FULV_.26_Edrecolomab_999|FULV & Edrecolomab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2009 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second'''
+*[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> 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'''
+</div></div>
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
+===References===
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first'''
+#'''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. [https://doi.org/10.1200/JCO.1993.11.10.1879 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8410113/ PubMed]
+##'''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. [https://doi.org/10.1245/s10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144/ PubMed]
-'''14-day cycle for 12 cycles'''
+#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. [https://doi.org/10.1016/0016-5085(94)90748-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8143995/ PubMed]
+#'''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. [https://doi.org/10.1200/jco.1997.15.1.246 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8996149/ PubMed]
+##'''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. [https://doi.org/10.1200/JCO.1999.17.5.1356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334519/ PubMed]
+#'''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. [https://doi.org/10.1093/jnci/90.23.1810 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9839521/ PubMed]
+##'''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. [https://doi.org/10.1245/s10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144/ PubMed]
+#'''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. [https://doi.org/10.1200/JCO.1999.17.11.3553 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10550154/ PubMed] [https://clinicaltrials.gov/study/NCT00425152 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. [https://doi.org/10.1245/s10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144/ PubMed]
+#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. [https://doi.org/10.1159/000012105 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10765125/ PubMed]
+#'''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. [https://doi.org/10.1016/s0140-6736(02)09836-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12241873/ PubMed]
+#'''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. [https://doi.org/10.1200/JCO.2003.10.065 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12885807/ PubMed]
+##'''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. [https://doi.org/10.1200/JCO.2007.12.2234 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17704423/ PubMed]
+#'''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. [https://doi.org/10.1056/NEJMoa032709 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15175436/ PubMed] [https://clinicaltrials.gov/study/NCT00275210 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. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431/ PubMed]
+##'''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. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776/ PubMed]
+#'''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. [https://doi.org/10.1056/NEJMoa043116 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15987918/ PubMed] [https://clinicaltrials.gov/study/NCT00009737 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. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539/ PubMed]
+<!-- Presented in part at the 33rd Annual Meeting of the American Society of Clinical Oncology, Denver, CO, May 20, 1997. -->
+#'''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. [https://doi.org/10.1200/jco.2004.00.5686 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16314627/ PubMed]
+<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 13-17, 2004. -->
+#'''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. [https://doi.org/10.1200/jco.2005.04.7498 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648506/ PubMed] [https://clinicaltrials.gov/study/NCT00378716 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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17194911/ PubMed] [https://clinicaltrials.gov/study/NCT00069121 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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21383294/ PubMed]
+##'''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. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362/ PubMed]
+#'''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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17470851/ PubMed] [https://clinicaltrials.gov/study/NCT00004931 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. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995/ PubMed]
+#'''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. [https://doi.org/10.1200/JCO.2007.11.2144 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17687149/ PubMed] [https://clinicaltrials.gov/study/NCT00003835 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. [https://doi.org/10.1016/j.ejca.2008.07.002 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18707870/ PubMed]
+#'''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. [https://doi.org/10.1093/annonc/mdn680 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19179549/ PubMed] [https://clinicaltrials.gov/study/NCT00005979 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. [https://doi.org/10.1200/JCO.2008.18.5710 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19273708/ PubMed]
+#'''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. [https://doi.org/10.1200/JCO.2008.21.6663 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19451425/ PubMed] [https://clinicaltrials.gov/study/NCT00026273 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. [https://doi.org/10.1186/1741-7015-9-10 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21281463/ PubMed] 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. [https://doi.org/10.1016/j.ejca.2013.01.030 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23571150/ PubMed] [https://clinicaltrials.gov/study/NCT00004150 NCT00004150]
-===Regimen variant #6, 2125/100 ("Mayo Clinic regimen") {{#subobject:4bd336|Variant=1}}===
+==S-1 monotherapy {{#subobject:5gh25a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:8cug1c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-||[https://www.nejm.org/doi/full/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ Yoshida et al. 2014 (ACTS-CC)]
-|1998-2001
+|2008-04 to 2009-06
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Capecitabine_monotherapy|Capecitabine]]
+|[[#Tegafur.2C_Uracil.2C_Folinic_acid|UFT + LV]]
-| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
+| style="background-color:#eeee01" |Non-inferior DFS36 (primary endpoint)<br>DFS36: 75.5% vs 72.5%<br>(HR 0.85, 95% CI 0.70-1.03)
-|-
-|[https://www.ejcancer.com/article/S0959-8049(08)00535-2/fulltext Popov et al. 2008 (PETACC-1)]
-|NR-1999
-| style="background-color:#1a9851" |Phase 3 (C)
-|Raltitrexed
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS/OS
-|-
-|[https://www.ejcancer.com/article/S0959-8049(13)00094-4/fulltext Köhne et al. 2013 (PETACC-2)]
-|1999-2004
-| style="background-color:#1a9851" |Phase 3 (C)
-|1. LV5FU2<br> 2. AIO regimen<br> 3. TTD regimen
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60
-|-
-|[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
-|2003-2004
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CapeOx|XELOX]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup>
 |-
 |}
-''<sup>1</sup>X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.''<br>
+<div class="toccolours" style="background-color:#cbd5e8">
-''<sup>2</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br>
-''Dosing details for PETACC-1 could not be confirmed from the abstract.''
 ====Preceding treatment====
 *[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
-*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second'''
+**Less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
-*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first'''
+**BSA between 1.25 m<sup>2</sup> and 1.50 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
+**BSA greater than 1.50 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 28
-'''28-day cycle for 6 cycles'''
+'''42-day cycle for 4 cycles'''
+</div></div>
-===Regimen variant #7, 2125/100, with cycle elongation ("Mayo Clinic regimen") {{#subobject:e24014|Variant=1}}===
+===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. [https://doi.org/10.1093/annonc/mdu232 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24942277/ PubMed] [https://clinicaltrials.gov/study/NCT00660894 NCT00660894]
+==SOX {{#subobject:617cc1|Regimen=1}}==
+SOX: '''<u>S</u>'''-1, '''<u>OX</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:c80e20|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1997.15.1.246 O'Connell et al. 1997]
+|[https://doi.org/10.1016/j.clcc.2019.10.002 Sunami et al. 2019 (ACTS-CC 02)]
-|1988-1989
+|2010-2014
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Colon_cancer_-_null_regimens#Observation|Observation]]
+|[[Colon_cancer#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic Acid]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
-| rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)]
+|}
-|rowspan=3|1988-1992
+<div class="toccolours" style="background-color:#cbd5e8">
-| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
+====Preceding treatment====
-|1. [[#FULV|FULV]]; high-dose
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+</div>
-|-
+<div class="toccolours" style="background-color:#b3e2cd">
-|2. LDLV & Levamisole
+====Chemotherapy====
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-|-
+*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
-|3. 5-FU & Levamisole
+'''21-day cycle for 8 cycles'''
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+</div></div>
-|-
+===References===
-| rowspan="2" |[https://www.thelancet.com/journals/lancet/article/PIIS0140673602098367/fulltext Punt et al. 2002 (Study 157-002)]
+#'''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. [https://doi.org/10.1016/j.clcc.2019.10.002 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073
-|rowspan=2|1995-1999
+##'''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. [https://doi.org/10.1016/j.esmoop.2021.100077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7966838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33714860/ PubMed]
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. FULV & Edrecolomab
+==Tegafur, Uracil, Folinic acid {{#subobject:5ed2aa|Regimen=1}}==
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+UFT + LV: '''<u>UFT</u>''' (Tegafur and uracil) & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|2. [[Colon_cancer_-_historical#Edrecolomab_monotherapy|Edrecolomab]]
+===Regimen variant #1, 300/75 {{#subobject:8cc7d8|Variant=1}}===
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://doi.org/10.1200/JCO.2008.18.5710 Fields et al. 2009 (Study 157-001)]
-|1995-1999
-| style="background-color:#1a9851" |Phase 3 (C)
-|FULV & Edrecolomab
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second'''
-*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> 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'''
-===Regimen variant #8, 2800/400 (LV5FUs) {{#subobject:476348|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1093/annonc/mdp236 Ychou et al. 2009]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621030/ Sadahiro et al. 2015 (JFMC33-0502)]
-|2001-2006
+|2005-2007
 | style="background-color:#1a9851" |Phase 3 (C)
-|FOLFIRI
+|[[#Tegafur.2C_Uracil.2C_Folinic_acid|UFT + LV]]; weekly x 18 mo
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ Yoshida et al. 2014 (ACTS-CC)]
+|2008-04 to 2009-06
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#S-1_monotherapy|S-1]]
+| style="background-color:#eeee01" |Non-inferior DFS36
+|-
+|[https://doi.org/10.1016/j.clcc.2019.10.002 Sunami et al. 2019 (ACTS-CC 02)]
+|2010-2014
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#SOX|SOX]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |}
-====Preceding treatment====
+''Note: In ACTS-CC, this dosing was used for patients with BSA less than 1.17 m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Surgery#Colorectal_cancer_surgery|Complete surgical resection of colorectal liver metastases]]
 ====Chemotherapy====
+*[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> 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'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+===Regimen variant #2, 300/90 {{#subobject:643dbb|Variant=1}}===
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first'''
-'''14-day cycle for 12 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. [https://doi.org/10.1200/JCO.1993.11.10.1879 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/8410113 PubMed]
-##'''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. [https://link.springer.com/article/10.1245%2Fs10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144 PubMed]
-#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. [https://doi.org/10.1200/jco.1997.15.1.246 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/8996149 PubMed]
-##'''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. [https://doi.org/10.1200/JCO.1999.17.5.1356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334519 PubMed]
-#'''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. [https://academic.oup.com/jnci/article/90/23/1810/2520545 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9839521 PubMed]
-##'''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. [https://link.springer.com/article/10.1245%2Fs10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144 PubMed]
-#'''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. [https://doi.org/10.1200/JCO.1999.17.11.3553 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10550154 PubMed] 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. [https://link.springer.com/article/10.1245%2Fs10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144 PubMed]
-#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. [https://www.karger.com/Article/Abstract/12105 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/10765125 PubMed]
-#'''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. [https://www.thelancet.com/journals/lancet/article/PIIS0140673602098367/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12241873 PubMed]
-#'''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. [https://doi.org/10.1200/JCO.2003.10.065 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12885807 PubMed]
-##'''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. [https://doi.org/10.1200/JCO.2007.12.2234 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17704423 PubMed]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa032709 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15175436 PubMed] 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. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431 PubMed]
-##'''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. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776 PubMed]
-#'''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. [https://www.nejm.org/doi/full/10.1056/NEJMoa043116 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15987918 PubMed] 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. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539 PubMed]
-<!-- Presented in part at the 33rd Annual Meeting of the American Society of Clinical Oncology, Denver, CO, May 20, 1997. -->
-#'''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. [https://doi.org/10.1200/jco.2004.00.5686 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16314627 PubMed]
-<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 13-17, 2004. -->
-#'''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. [https://doi.org/10.1200/jco.2005.04.7498 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16648506 PubMed] 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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17194911 PubMed] 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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/21383294/ PubMed]
-##'''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. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362 PubMed]
-#'''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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/17470851 PubMed] 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. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995 PubMed]
-#'''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. [https://doi.org/10.1200/JCO.2007.11.2144 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17687149 PubMed] 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. [https://www.ejcancer.com/article/S0959-8049(08)00535-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/18707870 PubMed]
-#'''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. [https://doi.org/10.1093/annonc/mdn680 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/19179549 PubMed] 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. [https://doi.org/10.1200/JCO.2008.18.5710 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/19273708 PubMed]
-#'''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. [https://doi.org/10.1200/JCO.2008.21.6663 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/19451425 PubMed] NCT00026273
-#Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009 Dec;20(12):1964-70. Epub 2009 Jun 30. [https://doi.org/10.1093/annonc/mdp236 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/19567451 PubMed]
-#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. [https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-10 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/21281463 PubMed] 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. [https://www.ejcancer.com/article/S0959-8049(13)00094-4/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/23571150 PubMed] NCT00004150
-==FULV (L-Leucovorin) {{#subobject:a93a7t|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FULV (L-Leucovorin): 5-'''<u>FU</u>''' & Levo'''<u>L</u>'''euco'''<u>V</u>'''orin
-===Regimen variant #1, 370/25, weekly {{#subobject:1d257d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02214-5/fulltext Gray et al. 2000 (QUASAR)]
+|[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)]
-|rowspan=2|1994-1997
+|1997-1999
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|1. FULV; HDLV
+|[[#FULV|FULV]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
-|-
-|2. FULV & Levamisole; LDLV<br> 3. FULV & Levamisole; HDLV
-| style="background-color:#d9ef8b" |Might have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*A potentially curative [[Surgery#Colorectal_cancer_surgery|resection]] of stage II or stage III colon cancer
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28
-*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Leucovorin (Folinic acid)]] 30 mg PO every 8 hours on days 1 to 28
-*[[Levoleucovorin (Fusilev)]] 25 mg/m<sup>2</sup> IV bolus once on day 1
+*No food for 1 hour before and after each dose of medication.
+'''35-day cycle for 5 cycles'''
-'''7-day cycle for 30 cycles'''
+</div></div>
-===Regimen variant #2, 1850/125, q4wk {{#subobject:acc8d1|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02214-5/fulltext Gray et al. 2000 (QUASAR)]
-|rowspan=2|1994-1997
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. FULV; HDLV
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|2. FULV & Levamisole; LDLV<br> 3. FULV & Levamisole; HDLV
-| style="background-color:#d9ef8b" |Might have superior OS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Levoleucovorin (Fusilev)]] 25 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-'''28-day cycle for 6 cycles'''
 ===References===
-#'''QUASAR:''' Gray RG, Kerr DJ, McConkey CC, Williams NS, Hills RK; QUASAR Collaborative Group. Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. Lancet. 2000 May 6;355(9215):1588-96. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02214-5/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10821362 PubMed] NCT00005586
+<!-- Presented at
-##'''Update:''' Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ; Quasar Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61866-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083404 PubMed]
-==SOX {{#subobject:617cc1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-SOX: '''<u>S</u>'''-1, '''<u>OX</u>'''aliplatin
-===Regimen {{#subobject:c80e20|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.clinical-colorectal-cancer.com/article/S1533-0028(19)30449-9/abstract Sunami et al. 2019 (ACTS-CC 02)]
-|2010-2014
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Colon_cancer#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic Acid]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Colorectal_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> 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. [https://www.clinical-colorectal-cancer.com/article/S1533-0028(19)30449-9/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073
-==Tegafur, Uracil, Folinic acid {{#subobject:5ed2aa|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-UFT + LV: '''<u>UFT</u>''' (Tegafur and uracil) & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
-===Regimen variant #1, 300/75 {{#subobject:8cc7d8|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ejcancer.com/article/S0959-8049(14)00724-2/fulltext Shimada et al. 2014 (JCOG0205)]
-|2003-2006
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#FULV|FULV]]
-| style="background-color:#eeee01" |Non-inferior DFS<br>(HR 1.02, 91.3% CI 0.84-1.23)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010179/ Hasegawa et al. 2016]
-|2004-2010
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Colon_cancer_-_null_regimens#Observation|Observation]]
-| style="background-color:#1a9850" |Superior RFS<br>Median RFS: 1.45 vs 0.7 yrs<br>(HR 0.56, 95% CI 0.38-0.83)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621030/ Sadahiro et al. 2015 (JFMC33-0502)]
-|2005-2007
-| style="background-color:#1a9851" |Phase 3 (C)
-|UFT + LV weekly x 18 mo
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ Yoshida et al. 2014 (ACTS-CC)]
-|2008-2009
-| style="background-color:#1a9851" |Phase 3 (C)
-|S-1
-| style="background-color:#eeee01" |Non-inferior DFS
-|-
-|[https://link.springer.com/article/10.1007%2Fs00595-017-1555-1 Miyake et al. 2018 (MCSGO-CCTG-0501)]
-|2006-2010
-| style="background-color:#1a9851" |Phase 3 (C)
-|UFT/PSK
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
-|-
-|[https://www.clinical-colorectal-cancer.com/article/S1533-0028(19)30449-9/abstract Sunami et al. 2019 (ACTS-CC 02)]
-|2010-2014
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#SOX|SOX]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|-
-|}
-''Note: Miyake et al. 2018 does not contain treatment details in the abstract.''
-====Preceding treatment====
-*JCOG0205: [[Surgery#Colorectal_cancer_surgery|Surgery]] with D2/D3 lymph node dissection
-*Hasegawa et al. 2016: [[Surgery#Metastasectomy|Surgical resection of colorectal cancer liver metastases]], within 8 weeks
-====Chemotherapy====
-*[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28
-*[[Folinic acid (Leucovorin)]] 25 mg PO every 8 hours on days 1 to 28
-'''35-day cycle for 5 cycles'''
-===Regimen variant #2, 300/90 {{#subobject:643dbb|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)]
-|1997-1999
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#FULV|FULV]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
-|-
-|}
-====Preceding treatment====
-*A potentially curative [[Surgery#Colorectal_cancer_surgery|resection]] of stage II or stage III colon cancer
-====Chemotherapy====
-*[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28
-*[[Folinic acid (Leucovorin)]] 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===
-<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 13-17, 2004. -->
-#'''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. [https://doi.org/10.1200/jco.2005.04.7498 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16648506 PubMed] 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. [https://doi.org/10.1093/annonc/mdu232 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24942277 PubMed] NCT00660894
-#'''JCOG0205:''' Shimada Y, Hamaguchi T, Mizusawa J, Saito N, Kanemitsu Y, Takiguchi N, Ohue M, Kato T, Takii Y, Sato T, Tomita N, Yamaguchi S, Akaike M, Mishima H, Kubo Y, Nakamura K, Fukuda H, Moriya Y. Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205. Eur J Cancer. 2014 Sep;50(13):2231-40. Epub 2014 Jun 20. [https://www.ejcancer.com/article/S0959-8049(14)00724-2/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/24958736 PubMed] NCT00190515
-#'''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. [https://doi.org/10.1093/annonc/mdv358 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621030/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/26347106 PubMed] UMIN C000000245
-#Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Mizunuma N, Matsuyama Y, Watanabe T, Makuuchi M, Kokudo N. Adjuvant oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: A randomized controlled trial. PLoS One. 2016 Sep 2;11(9):e0162400. eCollection 2016. [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162400 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010179/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27588959 PubMed] UMIN C000000013
-##'''Update:''' Kokudo T, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Mizunuma N, Matsuyama Y, Ishihara S, Makuuchi M, Kokudo N, Hasegawa K. Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases. Surgery. 2021 Oct;170(4):1151-1154. doi: 10.1016/j.surg.2021.04.012. Epub 2021 May 22. [https://doi.org/10.1016/j.surg.2021.04.012 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34030885/ PubMed]
-#'''MCSGO-CCTG-0501:''' Miyake Y, Nishimura J, Kato T, Ikeda M, Tsujie M, Hata T, Takemasa I, Mizushima T, Yamamoto H, Sekimoto M, Nezu R, Doki Y, Mori M; Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO). Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG). Surg Today. 2018 Jan;48(1):66-72. Epub 2017 Jun 20. [https://link.springer.com/article/10.1007%2Fs00595-017-1555-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28634730 PubMed] NCT00385970
-#'''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. [https://www.clinical-colorectal-cancer.com/article/S1533-0028(19)30449-9/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073
-=Therapy for oligometastatic disease, including perioperative therapy and hyperthermic intra-peritoneal chemotherapy=
-==FOLFIRI {{#subobject:a051ec|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
-===Regimen {{#subobject:0e95b6|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[http://ar.iiarjournals.org/content/32/4/1387.long Fiorentini et al. 2012]
-|2006-2008
-| style="background-color:#1a9851" |Phase 3 (C)
-|DEBIRI
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|}
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second on day 1''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 100 mg/m<sup>2</sup> IV over 120 minutes once on day 1, '''given first, with irinotecan'''
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 120 minutes once on day 1, '''given first, with leucovorin'''
-'''14-day cycle for 8 cycles'''
-===References===
-#Fiorentini G, Aliberti C, Tilli M, Mulazzani L, Graziano F, Giordani P, Mambrini A, Montagnani F, Alessandroni P, Catalano V, Coschiera P. Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study. Anticancer Res. 2012 Apr;32(4):1387-95. Erratum in: Anticancer Res. 2013 Nov;33(11):5211. [http://ar.iiarjournals.org/content/32/4/1387.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/22493375 PubMed]
-==FOLFOX4 {{#subobject:58d3ec|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FOLFOX4: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-===Regimen {{#subobject:dfc57d|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277487/ Nordlinger et al. 2008 (EORTC 40983)]
-|2000-2004
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Colon_cancer_-_null_regimens#Observation_3|Observation]]
-| style="background-color:#1a9850" |Superior PFS
-|-
-|[https://doi.org/10.1093/annonc/mdu539 Hebbar et al. 2014 (MIROX)]
-|2004-2010
-| style="background-color:#1a9851" |Phase 3 (C)
-|FOLFOX7-FOLFIRI
-| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS24
-|-
-|}
-''Note: this is the regimen as described by de Gramont et al. 2000; [[Study_Groups#EORTC|EORTC]] 40983 refers to this protocol. In MIROX, the treatment could be given perioperatively or postoperatively.''
-====Preceding treatment====
-*[[Surgery#Surgical_resection|Surgical resection of oligometastatic disease]]
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first, with oxaliplatin on day 1'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with leucovorin'''
-'''14-day cycle for 6 cycles before surgery, and 6 cycles after surgery (12 cycles total)'''
-===References===
-#'''EORTC 40983:''' Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; [[Study_Groups#EORTC|EORTC]] Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie; Australasian Gastro-Intestinal Trials Group; Fédération Francophone de Cancérologie Digestive. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007-16. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60455-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277487/ link to PMC article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/18358928 PubMed] NCT00006479
-##'''Update:''' Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Mauer M, Tanis E, Van Cutsem E, Scheithauer W, Gruenberger T; [[Study_Groups#EORTC|EORTC]] Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie; Australasian Gastro-Intestinal Trials Group; Fédération Francophone de Cancérologie Digestive. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectalcancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. Epub 2013 Oct 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70447-9/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/24120480 PubMed]
-#'''MIROX:''' Hebbar M, Chibaudel B, André T, Mineur L, Smith D, Louvet C, Dutel JL, Ychou M, Legoux JL, Mabro M, Faroux R, Auby D, Brusquant D, Khalil A, Truant S, Hadengue A, Dalban C, Gayet B, Paye F, Pruvot FR, Bonnetain F, Landi B, Flesch M, Carola E, Martin P, Vaillant
+=Advanced or metastatic disease=
+''See the [[Colorectal cancer|colorectal cancer page]] for colorectal cancer regimens.''
 [[Category:Colon cancer regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Colorectal cancers]]

Difference between revisions of "Colon cancer"

Latest revision as of 18:17, 21 July 2024

Guidelines

ASCO

ESMO

NCCN

Perioperative therapy

mFOLFOX6 (L-Leucovorin)

Neoadjuvant

Chemotherapy

Definitive

Local therapy

Adjuvant

Chemotherapy

References

Adjuvant therapy

Capecitabine monotherapy

Regimen

Preceding treatment

Chemotherapy

References

CapeOx

Example orders

Regimen variant #1, 3 months

Preceding treatment

Chemotherapy

Regimen variant #2, 6 months

Preceding treatment

Chemotherapy

References

FLOX

Example orders

Regimen

Preceding treatment

Chemotherapy

References

FOLFOX4

Regimen

Preceding treatment

Chemotherapy

References

mFOLFOX6

Example orders

Regimen

Preceding treatment

Chemotherapy

References

mFOLFOX6 (L-Leucovorin)

Example orders

Regimen variant #1, 3 months, 200 mg/m2 L-LCV

Preceding treatment

Chemotherapy

Regimen variant #2, 6 months, 200 mg/m2 L-LCV

Preceding treatment

Chemotherapy

References

FULV

Example orders

Regimen variant #1, 500/200, 6 out of 8 weeks

Preceding treatment

Chemotherapy

Regimen variant #2, 500/500, 6 out of 8 weeks

Preceding treatment

Chemotherapy

Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen")

Preceding treatment

Chemotherapy

Regimen variant #4, 1850/100 ("Mayo Clinic regimen")

Preceding treatment

Chemotherapy

Regimen variant #5, 1850/2500 ("NCI schedule")

Preceding treatment

Chemotherapy

Regimen variant #6, 2000/400 ("de Gramont regimen"/LV5FU2)

Preceding treatment

Chemotherapy

Regimen variant #7, 2000/1000

Preceding treatment

Chemotherapy

Regimen variant #8, 2125/100 ("Mayo Clinic regimen")

Regimen variant #1, 3 months, 200 mg/m² L-LCV

Regimen variant #2, 6 months, 200 mg/m² L-LCV