Colon cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main colon cancer page for current regimens.

10 regimens on this page
10 variants on this page


Adjuvant therapy

Bacillus Calmette-Guérin (BCG) monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Mavligit et al. 1976 Phase III (C) 5-FU & BCG Not reported

Immunotherapy

References

  1. Mavligit GM, Gutterman JU, Burgess MA, Khankhanian N, Seibert GB, Speer JF, Jubert AV, Martin RC, McBride CM, Copeland EM, Gehan EA, Hersh EM. Prolongation of postoperative disease-free interval and survival in human colorectal cancer by BCG or BCG plus 5-fluorouracil. Lancet. 1976 Apr 24;1(7965):871-6. link to original article PubMed
  2. NSABP C-01: Wolmark N, Fisher B, Rockette H, Redmond C, Wickerham DL, Fisher ER, Jones J, Glass A, Lerner H, Lawrence W, Prager D, Wexler M, Evans J, Cruz A, Dimitrov N, Jochimsen P; Other NSABP Investigators. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst. 1988 Mar 2;80(1):30-6. link to original article PubMed
    1. Update: Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. link to original article PubMed
    2. 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

Edrecolomab monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Riethmüller et al. 1994 Phase III (E) Observation Seems to have superior OS
Punt et al. 2002 (Study 157-002) Phase III (E) 1. 5-FU & LV Seems to have inferior OS
2. 5-FU, LV, Edrecolomab Not reported
Niedzwiecki et al. 2011 (CALGB 9581) Phase III (E) Observation Seems not superior

Note: this was the first monoclonal antibody approved (in Germany) for the therapeutic treatment of cancer; it was never FDA approved and was subsequently removed from the German market.

Preceding treatment

Chemotherapy

References

  1. Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Höffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J; German Cancer Aid 17-1A Study Group. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. Lancet. 1994 May 14;343(8907):1177-83. link to original article PubMed
  2. 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 PubMed
  3. CALGB 9581: Niedzwiecki D, Bertagnolli MM, Warren RS, Compton CC, Kemeny NE, Benson AB 3rd, Eckhardt SG, Alberts S, Porjosh GN, Kerr DJ, Fields A, Rougier P, Pipas JM, Schwartz JH, Atkins J, O'Rourke M, Perry MC, Goldberg RM, Mayer RJ, Colacchio TA. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol. 2011 Aug 10;29(23):3146-52. Epub 2011 Jul 11. link to original article link to PMC article PubMed

Fluorouracil monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Li & Ross 1976 Phase III (E) Observation Superior DFS
De Placido et al. 2005 (IGCS-COL) Phase III (C) 1. FULV
2. 5-FU & LEV
3. FULV & LEV
Seems not superior

Preceding treatment

Chemotherapy

References

  1. Li MC, Ross ST. Chemoprophylaxis for patients with colorectal cancer: prospective study with five-year follow-up. JAMA. 1976 Jun 28;235(26):2825-8. link to original article PubMed
  2. IGCS-COL: De Placido S, Lopez M, Carlomagno C, Paoletti G, Palazzo S, Manzione L, Iannace C, Ianniello GP, De Vita F, Ficorella C, Farris A, Pistillucci G, Gemini M, Cortesi E, Adamo V, Gebbia N, Palmeri S, Gallo C, Perrone F, Persico G, Bianco AR. Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study. Br J Cancer. 2005 Oct 17;93(8):896-904. link to original article link to PMC article PubMed

Fluorouracil & Levamisole

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Regimen

Study Evidence Comparator Comparative Efficacy
Moertel et al. 1990 Phase III (E) Observation Superior OS
O'Connell et al. 1998 Phase III (C) 5-FU, Leucovorin, Levamisole Inferior OS
Wolmark et al. 1999 (NSABP C-04) Phase III (C) 1. 5-FU & Leucovorin Might have inferior OS
2. 5-FU, Leucovorin, Levamisole Not reported
Taal et al. 2001 Phase III (E) Observation Superior OS
Dencausse et al. 2002 Phase III (C) 5-FU & Leucovorin Seems not superior
Martenson et al. 2004 (INT-0130) Phase III (C) 5-FU, LEV, RT Seems not superior
Glimelius et al. 2005 Phase III (E) Observation Seems not superior
Schippinger et al. 2005 (ABCSG Study 90) Phase III (E) 1. 5-FU
2. 5-FU & IFN alfa
Inferior OS
3. 5-FU, IFN alfa, Levamisole Seems not superior
Nordlinger et al. 2005 (FFCD 9204) Phase III (C) 5-FU, LEV, regional chemotherapy Seems not superior

Note: there was no statistical difference in the overall population of Glimelius et al. 2005; stage III patients appeared to derive benefit.

Preceding treatment

Chemotherapy

Immunotherapy

References

  1. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. link to original article PubMed
    1. Update: Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. link to original article PubMed
  2. O'Connell MJ, Laurie JA, Kahn M, Fitzgibbons RJ Jr, Erlichman C, Shepherd L, Moertel CG, Kocha WI, Pazdur R, Wieand HS, Rubin J, Vukov AM, Donohue JH, Krook JE, Figueredo A. Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer. J Clin Oncol. 1998 Jan;16(1):295-300. link to original article PubMed
  3. 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 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
  4. Taal BG, Van Tinteren H, Zoetmulder FA; NACCP group. Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III. Br J Cancer. 2001 Nov 16;85(10):1437-43. link to original article link to PMC article PubMed
  5. Dencausse Y, Hartung G, Sturm J, Kopp-Schneider A, Hagmüller E, Wojatschek C, Lindemann H, Fritze D, Queisser W. Adjuvant chemotherapy in stage III colon cancer with 5-fluorouracil and levamisole versus 5-fluorouracil and leucovorin. Oncology. 2002 Oct; 25 (5): 426-30. link to original article PubMed
  6. INT-0130: Martenson JA Jr, Willett CG, Sargent DJ, Mailliard JA, Donohue JH, Gunderson LL, Thomas CR Jr, Fisher B, Benson AB 3rd, Myerson R, Goldberg RM. Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130. J Clin Oncol. 2004 Aug 15;22(16):3277-83. Epub 2004 Jul 12. link to original article PubMed
  7. Glimelius B, Dahl O, Cedermark B, Jakobsen A, Bentzen SM, Starkhammar H, Grönberg H, Hultborn R, Albertsson M, Påhlman L, Tveit KM; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Acta Oncol. 2005;44(8):904-12. Erratum in: Acta Oncol. 2006;45(1):110. link to original article PubMed
    1. Update: Dahl O, Fluge Ø, Carlsen E, Wiig JN, Myrvold HE, Vonen B, Podhorny N, Bjerkeset O, Eide TJ, Halvorsen TB, Tveit KM; Norwegian Gastrointestinal Cancer Group. Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Norwegian Gastrointestinal Cancer Group. Acta Oncol. 2009;48(3):368-76. link to original article PubMed
  8. ABCSG Study 90: Schippinger W, Jagoditsch M, Sorré C, Gnant M, Steger G, Hausmaninger H, Mlineritsch B, Schaberl-Moser R, Mischinger HJ, Hofbauer F, Holzberger P, Mittlböck M, Jakesz R; Austrian Breast and Colorectal Cancer Study Group. A prospective randomised trial to study the role of levamisole and interferon alfa in an adjuvant therapy with 5-FU for stage III colon cancer. Br J Cancer. 2005 May 9;92(9):1655-62. link to original article link to PMC article PubMed
  9. FFCD 9204: Nordlinger B, Rougier P, Arnaud JP, Debois M, Wils J, Ollier JC, Grobost O, Lasser P, Wals J, Lacourt J, Seitz JF, Guimares dos Santos J, Bleiberg H, Mackiewickz R, Conroy T, Bouché O, Morin T, Baila L, van Cutsem E, Bedenne L. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial. Lancet Oncol. 2005 Jul;6(7):459-68. link to original article PubMed

Fluorouracil, Folinic acid, Levamisole

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Regimen

Study Evidence Comparator Comparative Efficacy
O'Connell et al. 1998 Phase III (E) 5-FU & Levamisole Superior OS
Poplin et al. 2005 (SWOG S9415) Phase III (C) CIFU & Levamisole Seems not superior

Preceding treatment

Chemotherapy

Immunotherapy

References

  1. O'Connell MJ, Laurie JA, Kahn M, Fitzgibbons RJ Jr, Erlichman C, Shepherd L, Moertel CG, Kocha WI, Pazdur R, Wieand HS, Rubin J, Vukov AM, Donohue JH, Krook JE, Figueredo A. Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer. J Clin Oncol. 1998 Jan;16(1):295-300. link to original article PubMed
  2. 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 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
  3. SWOG S9415: Poplin EA, Benedetti JK, Estes NC, Haller DG, Mayer RJ, Goldberg RM, Weiss GR, Rivkin SE, Macdonald JS. Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer. J Clin Oncol. 2005 Mar 20;23(9):1819-25. link to original article PubMed
  4. IGCS-COL: De Placido S, Lopez M, Carlomagno C, Paoletti G, Palazzo S, Manzione L, Iannace C, Ianniello GP, De Vita F, Ficorella C, Farris A, Pistillucci G, Gemini M, Cortesi E, Adamo V, Gebbia N, Palmeri S, Gallo C, Perrone F, Persico G, Bianco AR. Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study. Br J Cancer. 2005 Oct 17;93(8):896-904. link to original article link to PMC article PubMed

mFOLFOX6 & Bevacizumab

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mFOLFOX6 & Bevacizumab: FOLinic acid, Fluorouracil, OXaliplatin, Bevacizumab

Regimen

Study Evidence Comparator Comparative Efficacy
Allegra et al. 2009 (NSABP C-08) Phase III (E) mFOLFOX6 Seems not superior

Note: this was a negative experimental arm but is included for historic reference. Some guidelines do not recommend using bevacizumab as adjuvant therapy outside of a clinical trial.

Preceding treatment

Chemotherapy

14-day cycle for 12 cycles, to start within 10 weeks of surgery

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 verified protocol link to PMC article PubMed
    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. 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. link to original article link to PMC article PubMed

MOF

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MOF: MeCCNU (Semustine), Oncovin (Vincristine), Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Wolmark et al. 1988 (NSABP C-01) Phase III (E) 1. Observation
2. BCG
Seems not superior (*)
Wolmark et al. 1993 (NSABP C-03) Phase III (C) 5-FU & LV Inferior OS

Note: Reported efficacy for NSABP C-01 is based on the 2004 update.

Preceding treatment

Chemotherapy

References

  1. NSABP C-01: Wolmark N, Fisher B, Rockette H, Redmond C, Wickerham DL, Fisher ER, Jones J, Glass A, Lerner H, Lawrence W, Prager D, Wexler M, Evans J, Cruz A, Dimitrov N, Jochimsen P; Other NSABP Investigators. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst. 1988 Mar 2;80(1):30-6. link to original article PubMed
    1. Update: Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. link to original article PubMed
    2. 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. 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 verified protocol PubMed

Metastatic disease, first-line

Best supportive care

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Regimen

Study Evidence Comparator Comparative Efficacy
Goldberg et al. 1995 Phase III (C) Octreotide Seems not superior
Smyth et al. 1995 (N-trial) Phase III (C) TCNU Seems not superior

No active treatment.

References

  1. Goldberg RM, Moertel CG, Wieand HS, Krook JE, Schutt AJ, Veeder MH, Mailliard JA, Dalton RJ; North Central Cancer Treatment Group and the Mayo Clinic. A phase III evaluation of a somatostatin analogue (octreotide) in the treatment of patients with asymptomatic advanced colon carcinoma. Cancer. 1995 Sep 15;76(6):961-6. link to original article PubMed
  2. Smyth JF, Hardcastle JD, Denton G, Alderson D, Grace RH, Mansi JL, Yosef HM, Nordle O, Lauri H, Wählby S. Two phase III trials of tauromustine (TCNU) in advanced colorectal cancer. Ann Oncol. 1995 Nov;6(9):948-9. link to original article PubMed

Fluorouracil & Methotrexate

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Regimen

Study Evidence Comparator Comparative Efficacy
Wils et al. 2003 Phase III (C) 5-FU, MTX, PALA Seems not superior

Chemotherapy

References

  1. Wils J, Blijham GH, Wagener T, De Greve J, Jansen RL, Kok TC, Nortier JW, Bleiberg H, Couvreur ML, Genicot B, Baron B; EORTC Gastrointestinal Group. High-dose 5-fluorouracil plus low dose methotrexate plus or minus low-dose PALA in advanced colorectal cancer: a randomised phase II-III trial of the EORTC Gastrointestinal Group. Eur J Cancer. 2003 Feb;39(3):346-52. link to original article PubMed

Fluorouracil & Mitomycin

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Regimen

Study Evidence Comparator Comparative Efficacy
Price et al. 2004 Phase III (C) Chronomodulated 5-FU & MMC Seems not superior

Chemotherapy

References

  1. Price TJ, Ross PJ, Hickish T, Tait D, Norman AR, Ford HE, Middleton G, Sumpter K, Hill M, Oates J, Cunningham D. Phase III study of mitomycin-C with protracted venous infusion or circadian-timed infusion of 5-fluorouracil in advanced colorectal carcinoma. Clin Colorectal Cancer. 2004 Feb;3(4):235-42. link to original article PubMed

Fluorouracil & Semustine

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Regimen

Study Evidence Comparator Comparative Efficacy
Baker et al. 1976 Phase III (C) 5-FU Superior ORR
Engstrom et al. 1982 (ECOG E4275) Phase III (E) 1. 5-FU, Semustine, Vincristine
2. 5-FU, Dacarbazine, Semustine
3. 5-FU, Dacarbazine, Semustine, Vincristine
4. 5-FU & Hydrea
Seems not superior

Chemotherapy

References

  1. Baker LH, Talley RW, Matter R, Lehane DE, Ruffner BW, Jones SE, Morrison FS, Stephens RL, Gehan EA, Vaitkevicius VK. Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5-FU vs methyl-CCNU plus bolus weekly 5-FU: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):1-7. link to original article PubMed
  2. ECOG E4275: Engstrom PF, MacIntyre JM, Douglass HO Jr, Muggia F, Mittelman A. Combination chemotherapy of advanced colorectal cancer utilizing 5-fluorouracil, semustine, dacarbazine, vincristine, and hydroxyurea: a phase III trial by the Eastern Cooperative Oncology Group (EST: 4275). Cancer. 1982 Apr 15;49(8):1555-60. link to original article PubMed

FOLFOX chronotherapy

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study Evidence Comparator Comparative Efficacy
Lévi et al. 1997 Phase III (E) FOLFOX CI Superior TTF

This schedule is "chronomodulated"; see paper for details.

Chemotherapy

21-day cycles

References

  1. Lévi F, Zidani R, Misset JL; International Organization for Cancer Chronotherapy. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet. 1997 Sep 6;350(9079):681-6. link to original article contains verified protocol PubMed