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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. 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 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)	NR-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)	NR-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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in abstract 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: Miyake et al. 2018 does not contain treatment details in the abstract.

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 contains dosing details in manuscript 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 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 contains dosing details in abstract 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 contains dosing details in manuscript 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: @@
+<span id="BackToTop"></span>
+<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">
+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|gi}}
+''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: 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.</big>
+*See the [[Colon_cancer,_RAS_wild-type|'''RAS wild-type page''']] for biomarker-specific adjuvant regimens.</big>
+{| class="wikitable" style="float:right; margin-right: 5px;"
+|-
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
+|}
 {{TOC limit|limit=3}}
+=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.'''
+==[http://www.asco.org/ ASCO]==
+*'''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]
+==[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] [https://www.ncbi.nlm.nih.gov/pubmed/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] [https://www.ncbi.nlm.nih.gov/pubmed/32702383 PubMed]
+**'''2013:''' Labianca et al. [https://doi.org/10.1093/annonc/mdt354 Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://www.ncbi.nlm.nih.gov/pubmed/24078664 PubMed]
+**'''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]
+**'''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]
+**'''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]
+*'''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://www.ncbi.nlm.nih.gov/pubmed/31378807 PubMed]
-==Adjuvant therapy==
+==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://pubmed.ncbi.nlm.nih.gov/19764149/ PubMed]
-===5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV)===
+=Perioperative therapy=
-====Regimen====
+==mFOLFOX6 (L-Leucovorin) {{#subobject:8uy6d7|Regimen=1}}==
-*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV push before 5-FU days 1-5
+mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-*[[Fluorouracil (5-FU)]] 425 mg/m2 IV push days 1-5
+<div class="toccolours" style="background-color:#c8a2c8">
+{| 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022855/ Morton et al. 2023 (FOxTROT)]
+|2008-05-15 to 2016-12-23
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#mFOLFOX6_.28L-Leucovorin.29_2|mFOLFOX6]]; adjuvant
+| 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)
+|-
+|}
+''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.''
+<div class="toccolours" style="background-color:#eeeeee">
+===Neoadjuvant {{#subobject:30juz2|Variant=1}}===
+<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 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/36657089/ PubMed] [https://clinicaltrials.gov/study/NCT00647530 NCT00647530]
-Two different schedules have been used:
+=Adjuvant therapy=
-#'''4-week cycles x 3 cycles, then 5-week cycles x 3 cycles'''
+==Capecitabine monotherapy {{#subobject:7b50df|Regimen=1}}==
-#'''4-week cycles x 6 cycles'''
+<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
+|-
+|}
+''<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] '''contains dosing details in manuscript''' [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]
+#'''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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6461756/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30833647/ PubMed]
-====References====
+==CapeOx {{#subobject:cf9acc|Regimen=1}}==
-# 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. [http://jco.ascopubs.org/content/15/1/246.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/8996149 PubMed]
+CapeOx: '''<u>Cape</u>'''citabine & '''<u>Ox</u>'''aliplatin
-# Twelves C, Wong A, Nowacki MP, Abt M, Burris H 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa043116 link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/15987918 PubMed]
+<br>CAPOX: '''<u>CAP</u>'''ecitabine & '''<u>OX</u>'''aliplatin
-# 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. [http://jco.ascopubs.org/content/23/34/8671.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/16314627 PubMed]
+<br>XELOX: '''<u>XEL</u>'''oda (Capecitabine) & '''<u>OX</u>'''aliplatin
-# 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. [http://jco.ascopubs.org/content/25/1/102.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/17194911 PubMed]
+===Example orders===
+*[[Example orders for CapeOx (XELOX) in colon cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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)]
+|2012-08-01 to 2014-06-30
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo
+| 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%"|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.2006.08.1075 Schmoll et al. 2007 (XELOXA)]
+|2003-04 to 2004-10
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+|[[#FULV|FULV]]
+| 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/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)]
+|2012-08-01 to 2014-06-30
+| style="background-color:#1a9851" |Phase 3 (C)
+|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.''
+<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>
-===5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV)===
+===References===
-====Regimen====
+#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17194911/ PubMed] [https://clinicaltrials.gov/study/NCT00069121 NCT00069121]
-*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours weekly x 6 weeks
+##'''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]
-*[[Fluorouracil (5-FU)]] 500 mg/m2 IV push 1 hour after start of leucovorin weekly x 6 weeks
+##'''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]
+##'''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]
+#'''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] '''contains dosing details in manuscript''' [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]
+#'''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]
+#'''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]
-'''8-week cycles x 4 cycles'''
+==FLOX {{#subobject:617cc1|Regimen=1}}==
+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%"|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.2006.08.2974 Kuebler et al. 2007 (NSABP C-07)]
+|2000-2002
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#FULV|FULV]]
+| 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'''
+*[[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] '''contains dosing details in manuscript''' [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]
+==FOLFOX4 {{#subobject:f61339|Regimen=1}}==
+FOLFOX4: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:671bbe|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/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> (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://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_.26_Bevacizumab_999|FOLFOX4 & Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|2. [[#CapeOx_.26_Bevacizumab_999|XELOX & Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|[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_.26_Cetuximab_999|FOLFOX4 & Cetuximab]]
+| 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
+|-
+|}
+''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2015 update.''<br>
+''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>)
+*[[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====
+===References===
-# 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. [http://jco.ascopubs.org/content/23/34/8671.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/16314627 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15175436/ PubMed] [https://clinicaltrials.gov/study/NCT00275210 NCT00275210]
-# 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. [http://jco.ascopubs.org/content/24/13/2059.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/16648506 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]
-# 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. [http://jco.ascopubs.org/content/25/1/102.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/17194911 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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23168362/ PubMed] [https://clinicaltrials.gov/study/NCT00112918 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]
+#'''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]
+#'''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]
+#'''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}}==
+mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<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 {{#subobject:30juz2|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ Allegra et al. 2009 (NSABP C-08)]
+|2004-2006
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Colon_cancer_-_historical#mFOLFOX6-B|mFOLFOX6-B]]
+| 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
+</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>)
+*[[Leucovorin (Folinic acid)]] 400 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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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]
-===Capecitabine (Xeloda)===
+==mFOLFOX6 (L-Leucovorin) {{#subobject:32d6d7|Regimen=1}}==
-====Regimen====
+mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
-*[[Capecitabine (Xeloda)]] 1250 mg/m2 PO BID days 1-14
+===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%"|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)]
+|2012-08-01 to 2014-06-30
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo
+| 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====
+*[[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'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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)]
+|2012-08-01 to 2014-06-30
+| style="background-color:#1a9851" |Phase 3 (C)
+|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]]
+</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>)
+*[[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>
+===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] '''contains dosing details in manuscript''' [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%"|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]
+|1999-2004
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#IFL_999|IFL]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
+|-
+|}
+<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 once per day on days 1, 8, 15, 22, 29, 36
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
+'''8-week cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-258-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
+|-
+|} -->
+|1987-1989
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[Colon_cancer_-_historical#MOF|MOF]]
+| 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]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/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-esc)
+|1. [[#FULV|FULV]]; low-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
+|-
+|[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]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
+|-
+|[https://doi.org/10.1200/JCO.2007.11.2144 Saltz et al. 2007 (CALGB 89803)]
+|1999-2001
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#IFL_999|IFL]]
+| 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)]
+|2000-2002
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#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 3 to 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''21-day cycles x 8 cycles'''
+===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%"|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]
+|1989-1997
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FULV_.26_Interferon_alfa-2a_999|FULV & IFN alfa-2a]]
+| 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'''
+*[[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 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 1850/100 ("Mayo Clinic regimen") {{#subobject:4bnc36|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/10.1016/j.ejca.2008.07.002 Popov et al. 2008 (PETACC-1)]
+|NR-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Raltitrexed_monotherapy_999|Raltitrexed]]
+| 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'''
+*[[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 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 1850/2500 ("NCI schedule") {{#subobject:7cc2b9|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://academic.oup.com/jnci/article/90/23/1810/2520545 Wolmark et al. 1998 (NSABP C-05)]
+|1991-1994
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FULV_.26_Interferon_alfa_999|FULV & Interferon alfa]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/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)]] 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]]
+|-
+|[https://doi.org/10.1200/JCO.2003.10.065 André et al. 2003 (GERCOR C96.1)]
+|1996-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FULV|FULV]]; monthly
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|[https://doi.org/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
+|1998-2001
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FOLFOX4|FOLFOX4]]
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+|-
+|[https://doi.org/10.1093/annonc/mdn680 Ychou et al. 2009 (FFCD 9802)]
+|1998-2002
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#IFL_999|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)]
+|2000-2002
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#IFL_999|IFL]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
+|-
+|}
+''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2015 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)]] 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>)
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first'''
+'''14-day cycle for 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #7, 2000/1000 {{#subobject:6igjc9|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/10.1016/0016-5085(94)90748-x Francini et al. 1994]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-259-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
+|-
+|} -->
+|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
+</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
+*[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
+'''28-day cycle for 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #8, 2125/100 ("Mayo Clinic regimen") {{#subobject:4bd336|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 (C)
+|[[#Capecitabine_monotherapy|Capecitabine]]
+| 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)]
+|NR-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'''
+*[[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 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-====References====
+===Regimen variant #9, 2125/100, with cycle elongation ("Mayo Clinic regimen") {{#subobject:e24014|Variant=1}}===
-# Twelves C, Wong A, Nowacki MP, Abt M, Burris H 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa043116 link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/15987918 PubMed]
+{| 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/10.1200/jco.1997.15.1.246 O'Connell et al. 1997 (CALGB 8896)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-260-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
+|-
+|} -->
+|1988-02 to 1989-08
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Colon_cancer_-_null_regimens#Observation|Observation]]
+| 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
+|-
+|2. [[Colon_cancer_-_historical#Edrecolomab_monotherapy|Edrecolomab]]
+| 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_.26_Edrecolomab_999|FULV & Edrecolomab]]
+| 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)]] 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>
-===CapeOx (XELOX)===
+===References===
-CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin <br>
+#'''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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8410113/ PubMed]
-XELOX: '''<u>XEL</u>'''oda, '''<u>OX</u>'''aliplatin
+##'''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/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]
+#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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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/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] '''contains dosing details in manuscript''' [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://link.springer.com/article/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://www.karger.com/Article/Abstract/12105 link to original article] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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 dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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 dosing details in abstract''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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 dosing details in abstract''' [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] '''contains dosing details in manuscript''' [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 dosing details in abstract''' [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://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 dosing details in abstract''' [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====
+==S-1 monotherapy {{#subobject:5gh25a|Regimen=1}}==
-*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID days 1-14
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours day 1
+===Regimen {{#subobject:8cug1c|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://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 (E-switch-ic)
+|[[#Tegafur.2C_Uracil.2C_Folinic_acid|UFT + LV]]
+| 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)
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====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:
+**Less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
+**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
+'''42-day cycle for 4 cycles'''
+</div></div>
+===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] '''contains dosing details in manuscript''' [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%"|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/10.1016/j.clcc.2019.10.002 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
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Colorectal_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====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'''
+</div></div>
+===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://doi.org/10.1016/j.clcc.2019.10.002 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073
+##'''Update:''' Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. [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]
-'''21-day cycles x 8 cycles'''
+==Tegafur, Uracil, Folinic acid {{#subobject:5ed2aa|Regimen=1}}==
+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">
+===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%"|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/PMC4621030/ Sadahiro et al. 2015 (JFMC33-0502)]
+|2005-2007
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#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
+|-
+|}
+''Note: Miyake et al. 2018 does not contain treatment details in the abstract.''
+<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
+*[[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">
-====References====
+===Regimen variant #2, 300/90 {{#subobject:643dbb|Variant=1}}===
-# 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. [http://jco.ascopubs.org/content/25/1/102.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/17194911 PubMed]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-# Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. [http://jco.ascopubs.org/content/26/12/2006.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/18421053 PubMed]
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-===FLOX===
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-====Regimen====
+!style="width: 20%"|Comparator
-*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus 1 hour after start of leucovorin weekly x 6 weeks
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours weekly x 6 weeks
+|-
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours on weeks 1, 3, 5; given prior to 5-FU and leucovorin
+|[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)]
+|1997-1999
-'''8-week cycles x 3 cycles'''
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#FULV|FULV]]
-====References====
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS
-# 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. [http://jco.ascopubs.org/content/25/16/2198.full link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/17470851 PubMed]
+|-
+|}
-===FOLFOX 4===
+<div class="toccolours" style="background-color:#cbd5e8">
-====Regimen====
+====Preceding treatment====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours; both bolus and continuous infusion given on days 1 & 2
+*A potentially curative [[Surgery#Colorectal_cancer_surgery|resection]] of stage II or stage III colon cancer
-*[[Folinic acid (Leucovorin)]] 200 mg/m2 IV over 2 hours before 5-FU on days 1 and 2
+</div>
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 in 250 mL of 5% dextrose IV over 2 hours concurrent with leucovorin day 1
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-'''14-day cycles x 12 cycles'''
+*[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28
+*[[Leucovorin (Folinic acid)]] 30 mg PO every 8 hours on days 1 to 28
-====References====
-# de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. [http://jco.ascopubs.org/content/18/16/2938.long link to original article ] '''(contains protocol)'''  [http://www.ncbi.nlm.nih.gov/pubmed/10944126 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa032709 link to original article ] '''(contains protocol)'''  [http://www.ncbi.nlm.nih.gov/pubmed/15175436 PubMed]
-# Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91.  [http://jco.ascopubs.org/content/24/25/4085.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16943526 PubMed]
-# Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. [http://jco.ascopubs.org/content/26/12/2006.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18421053 PubMed]
-===mFOLFOX 6===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours day 1
-'''14-day cycles x 12 cycles'''
-====References====
-# Kojima S, Ina K, Futamura Y, Ito Y, Hibi S, Nagaoka M, Yuasa S, Kawai M, Nagao S, Kataoka T. A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer. Gan To Kagaku Ryoho. 2007 Feb;34(2):203-6. [http://www.pieronline.jp/content/article/0385-0684/34020/203 link to original article (Japanese)] [http://www.ncbi.nlm.nih.gov/pubmed/17301527 PubMed]
-===FULV===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus 1 hour after start of leucovorin weekly x 6
-*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours weekly x 6
-'''8-week cycles x 3 cycles'''
-====References====
-# 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. [http://jco.ascopubs.org/content/25/16/2198.full link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/17470851 PubMed]
-===UFT & leucovorin===
-====Regimen====
-*[[Uracil-tegafur (UFT)]] 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) x 4 weeks
-*[[Folinic acid (Leucovorin)]] 30 mg PO Q8H (total dose of 90 mg/day) x 4 weeks
 *No food for 1 hour before and after each dose of medication.
+'''35-day cycle for 5 cycles'''
+</div></div>
+===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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648506/ PubMed] [https://clinicaltrials.gov/study/NCT00378716 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] [https://clinicaltrials.gov/study/NCT00660894 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. [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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26347106/ 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. [https://doi.org/10.1016/j.clcc.2019.10.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073
+##'''Update:''' Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. [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]
-'''5-week cycles x 5 cycles'''
+=Advanced or metastatic disease=
+''See the [[Colorectal cancer|colorectal cancer page]] for colorectal cancer regimens.''
-====References====
+[[Category:Colon cancer regimens]]
-# 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. [http://jco.ascopubs.org/content/24/13/2059.long link to original article] '''(contains protocol)''' [http://www.ncbi.nlm.nih.gov/pubmed/16648506 PubMed]
+[[Category:Disease-specific pages]]
+[[Category:Colorectal cancers]]
-==Advanced or metastatic disease==
-===mFOLFOX 6===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours day 1
-'''14-day cycles'''
-====References====
-# Kojima S, Ina K, Futamura Y, Ito Y, Hibi S, Nagaoka M, Yuasa S, Kawai M, Nagao S, Kataoka T. A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer. Gan To Kagaku Ryoho. 2007 Feb;34(2):203-6. [http://www.pieronline.jp/content/article/0385-0684/34020/203 link to original article (Japanese)] [http://www.ncbi.nlm.nih.gov/pubmed/17301527 PubMed]
-===mFOLFOX 6 & Bevacizumab (Avastin)===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours day 1
-*[[Bevacizumab (Avastin)]] 5 mg/kg IV day 1
-'''14-day cycles'''
-====References====
-===mFOLFOX 6 & Panitumumab (Vectibix)===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours day 1
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes day 1
-'''14-day cycles'''
-====References====
-===CapeOx (XELOX)===
-CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin <br>
-XELOX: '''<u>XEL</u>'''oda, '''<u>OX</u>'''aliplatin
-====Regimen====
-*[[Capecitabine (Xeloda)]] 850-1000 (however, lower dosages often used) mg/m2 PO BID on days 1-14
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
-'''21-day cycles'''
-====References====
-===CapeOX & Bevacizumab (Avastin)===
-CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin
-====Regimen====
-*[[Capecitabine (Xeloda)]] 850-1000 (however, lower dosages often used) mg/m2 PO BID on days 1-14
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
-*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV over 15 minutes on day 1
-'''21-day cycles'''
-====References====
-===FOLFIRI===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over a duration that matches irinotecan infusion day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes day 1
-'''14-day cycles'''
-====References====
-===FOLFIRI & Bevacizumab (Avastin)===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over a duration that matches irinotecan infusion day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes day 1
-*[[Bevacizumab (Avastin)]] 5 mg/kg IV day 1
-'''14-day cycles'''
-====References====
-===FOLFIRI & Cetuximab (Erbitux)===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over a duration that matches irinotecan infusion day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes day 1
-*EITHER [[Cetuximab (Erbitux)]] 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, [[Cetuximab (Erbitux)]] 250 mg/m2 IV over 60 minutes on days 1 & 8
-*OR [[Cetuximab (Erbitux)]] 500 mg/m2 IV over 2 hours on day 1
-'''14-day cycles'''
-'''Reference'''
-* Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd. SO. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(14):2311  PMID 18390971
-====References====
-===FOLFIRI & Panitumumab (Vectibix)===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over a duration that matches irinotecan infusion day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes day 1
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes day 1
-'''14-day cycles'''
-====References====
-===Capecitabine (Xeloda)===
-====Regimen====
-*[[Capecitabine (Xeloda)]] 850-1250 mg/m2 PO BID days 1-14
-'''21-day cycles'''
-====References====
-===Capecitabine (Xeloda) & Bevacizumab (Avastin)===
-====Regimen====
-*[[Capecitabine (Xeloda)]] 850-1250 mg/m2 PO BID days 1-14
-*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV over 15 minutes on day 1
-'''21-day cycles'''
-====References====
-===Bolus 5-FU & Leucovorin (Roswell Park regimen/HDLV)===
-====Regimen====
-*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours weekly x 6 weeks
-*[[Fluorouracil (5-FU)]] 500 mg/m2 IV push 1 hour after start of leucovorin weekly x 6 weeks
-'''8-week cycles'''
-====References====
-===Infusional 5-FU & Leucovorin (sLV5FU2)===
-====Regimen====
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours day 1 (administer first)
-*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus after leucovorin, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
-'''14-day cycles'''
-Alternate schedule #1:
-*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV over 2 hours day 1 (administer first)
-*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus 1 hour after start of leucovorin
-'''7-day cycles'''
-Alternate schedule #2:
-*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV day 1 (administer first)
-*[[Fluorouracil (5-FU)]] 2600 mg/m2 IV over 24 hours
-'''7-day cycles'''
-====References====
-===IROX===
-====Regimen====
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours on day 1 (administer first)
-*[[Irinotecan (Camptosar)]] 200 mg/m2 IV over 30-90 minutes day 1 (administer second)
-'''21-day cycles'''
-====References====
-===FOLFOXIRI===
-====Regimen====
-*[[Fluorouracil (5-FU)]] 3200 mg/m2 (total dose) IV over 48 hours on days 1-2
-*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV day 1
-*[[Irinotecan (Camptosar)]] 165 mg/m2 IV day 1
-'''14-day cycles'''
-====References====
-===Irinotecan (Camptosar)===
-====Regimen====
-*[[Irinotecan (Camptosar)]] 125 mg/m2 IV over 30-90 minutes on days 1 & 8
-'''21-day cycles'''
-Alternate schedule:
-*[[Irinotecan (Camptosar)]] 300-350 mg/m2 IV over 30-90 minutes on day 1
-'''21-day cycles'''
-====References====
-===Cetuximab (Erbitux) & Irinotecan (Camptosar)===
-====Regimen====
-*[[Cetuximab (Erbitux)]] 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days 8 & 15 of cycle 1; then on subsequent cycles, [[Cetuximab (Erbitux)]] 250 mg/m2 IV over 60 minutes on days 1, 8, 15
-*EITHER [[Irinotecan (Camptosar)]] 300-350 mg/m2 IV over 30-90 minutes on day 1
-*OR [[Irinotecan (Camptosar)]] 125 mg/m2 IV over 30-90 minutes on days 1 & 8
-'''21-day cycles'''
-Alternate schedule:
-*[[Cetuximab (Erbitux)]] 500 mg/m2 IV over 2 hours on day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes day 1
-'''14-day cycles'''
-====References====
-===Cetuximab (Erbitux)===
-====Regimen====
-*[[Cetuximab (Erbitux)]] 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days 8 of cycle 1; then on subsequent cycles, [[Cetuximab (Erbitux)]] 250 mg/m2 IV over 60 minutes on days 1 & 8
-'''14-day cycles'''
-Alternate schedule:
-*[[Cetuximab (Erbitux)]] 500 mg/m2 IV over 2 hours on day 1
-'''14-day cycles'''
-====References====
-===Panitumumab (Vectibix)===
-====Regimen====
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes day 1
-'''14-day cycles'''
-====References====

Difference between revisions of "Colon cancer"

Latest revision as of 17:45, 23 June 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