Colon cancer

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Section editor
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 Travis Zack, MD, PhD
University of California San Francisco
San Francisco, CA, USA
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Are you looking for a regimen, but can't find it here? 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.

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

ESMO

NCCN

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


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

  1. 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

Chemotherapy

21-day cycle for 8 cycles

References

  1. 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
  2. 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

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

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

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. CIRCULATE-IDEA: NCT05174169

FLOX

FLOX: Fluorouracil, Leucovorin, OXaliplatin

Example orders

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

Chemotherapy

8-week cycle for 3 cycles

References

  1. 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
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

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

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

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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

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

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

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

  1. 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

Chemotherapy

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)
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

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

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

Chemotherapy

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

Chemotherapy

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

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

Chemotherapy

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

Chemotherapy

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
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

Chemotherapy

28-day cycle for 3 cycles, then 35-day cycle for 3 cycles

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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

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

  1. 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

Chemotherapy

21-day cycle for 8 cycles

References

  1. 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

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

35-day cycle for 5 cycles

References

  1. 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
  2. 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
  3. 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
  4. 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.

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