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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main colon cancer page for current regimens.

Last updated on 2024-07-23:
7 regimens on this page
11 variants on this page


Adjuvant therapy

BCG vaccine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mavligit et al. 1976 1973-1975 Phase 3 (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; NSABP. 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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Riethmüller et al. 1994 1985-1990 Phase 3 (E-esc) Observation Seems to have superior OS
Punt et al. 2002 (Study 157-002) 1995-1999 Phase 3 (E-switch-ooc) 1. FULV Seems to have inferior OS
2. FULV & Edrecolomab Not reported
Niedzwiecki et al. 2011 (CALGB 9581) 1997-2002 Phase 3 (E-esc) Observation Did not meet primary endpoint of OS

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

Targeted therapy

  • Edrecolomab (Panorex) as follows:
    • Cycle 1: 500 mg IV over 120 minutes once on day 1
    • Cycles 2 to 5: 100 mg IV once on day 1

28-day cycle for 5 cycles

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 dosing details in manuscript have been reviewed by our editors PubMed NCT00002968


Fluorouracil monotherapy

Regimen variant #1, 6 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Li & Ross 1976 1965-1970 Phase 3 (E-esc) Observation Superior DFS
De Placido et al. 2005 (IGCS-COL) 1991-1998 Phase 3 (C) 1. FULV
2. 5-FU & LEV
3. FULV & LEV
Did not meet co-primary endpoints of DFS/OS

Preceding treatment

Chemotherapy

  • Fluorouracil (5-FU) as follows:
    • Cycle 1: 450 mg/m2 IV bolus once per day on days 1 to 5
    • Cycles 2 to 23: 450 mg/m2 IV bolus once on day 1

28-day course, then 7-day cycle for 22 cycles (6 months total)


Regimen variant #2, 12 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schippinger et al. 2005 (ABCSG Study 90) 1991-1999 Phase 3 (C) 1. 5-FU & Levamisole
2. 5-FU, IFN alfa, Levamisole
Superior OS (primary endpoint)
3. 5-FU & IFN alfa Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

  • Fluorouracil (5-FU) as follows:
    • Cycle 1: 450 mg/m2 IV bolus once per day on days 1 to 5
    • Cycles 2 to 49: 450 mg/m2 IV bolus once on day 1

28-day course, then 7-day cycle for 48 cycles (1 year total)

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. 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; ABCSG. 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 dosing details in manuscript have been reviewed by our editors PubMed
  3. 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 dosing details in manuscript have been reviewed by our editors PubMed


Fluorouracil & Levamisole

Regimen variant #1, 6 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
O'Connell et al. 1998 Not reported Phase 3 (C) FULV & Levamisole Inferior OS
Nordlinger et al. 2005 (FFCD 9204) 1993-1998 Phase 3 (C) 5-FU, LEV, regional chemotherapy Did not meet primary endpoint of OS60

Preceding treatment

Chemotherapy

  • Fluorouracil (5-FU) as follows:
    • Cycle 1: 450 mg/m2 IV once per day on days 1 to 5
    • Cycles 2 to 12: 450 mg/m2 IV once per day on days 1 & 8

Immunotherapy

  • Levamisole (Ergamisol) as follows:
    • Cycle 1: 50 mg PO three times per day on days 1 to 3, 15 to 17
    • Cycles 2 to 12: 50 mg PO three times per day on days 1 to 3

28-day course, then 14-day cycle for 11 cycles


Regimen variant #2, 12 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Laurie et al. 1989 Not reported Phase 3 (E-RT-esc) 1. Observation Seems to have superior OS
2. Levamisole Not reported
Moertel et al. 1990 (SWOG S8591) 1984-1987 Phase 3 (E-RT-esc) 1. Observation Superior OS
2. Levamisole Not reported
O'Connell et al. 1998 Not reported Phase 3 (C) FULV & Levamisole Inferior OS
Wolmark et al. 1999 (NSABP C-04) 1989-07 to 1990-12 Phase 3 (C) 1. FULV Might have inferior OS
2. FULV & Levamisole Not reported
Taal et al. 2001 1991-1996 Phase 3 (E-esc) Observation Superior OS
Glimelius et al. 2005 1991-1997 Phase 3 (E-esc) Observation Did not meet primary endpoint of OS
Schippinger et al. 2005 (ABCSG Study 90) 1991-1999 Phase 3 (E-esc) 1. 5-FU
2. 5-FU & IFN alfa
Inferior OS (primary endpoint)
3. 5-FU, IFN alfa, Levamisole Did not meet primary endpoint of OS
Martenson et al. 2004 (INT-0130) 1992-1996 Phase 3 (C) 5-FU, LEV, RT Did not meet primary endpoint of OS
Dencausse et al. 2002 1993-1997 Randomized (C) FULV Did not meet co-primary endpoints of DFS/OS

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

  • Fluorouracil (5-FU) as follows:
    • Cycle 1: 450 mg/m2 IV once per day on days 1 to 5
    • Cycles 2 to 25: 450 mg/m2 IV once per day on days 1 & 8

Immunotherapy

  • Levamisole (Ergamisol) as follows:
    • Cycle 1: 50 mg PO three times per day on days 1 to 3, 15 to 17
    • Cycles 2 to 25: 50 mg PO three times per day on days 1 to 3

28-day course, then 14-day cycle for 24 cycles (1 year total)


References

  1. Laurie JA, Moertel CG, Fleming TR, Wieand HS, Leigh JE, Rubin J, McCormack GW, Gerstner JB, Krook JE, Malliard J, Twito DI, Morton RF, Tschetter LK, Barlow JF; The North Central Cancer Treatment Group and the Mayo Clinic. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. J Clin Oncol. 1989 Oct;7(10):1447-56. link to original article dosing details in abstract have been reviewed by our editors PubMed
  2. SWOG S8591: 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 dosing details in manuscript have been reviewed by our editors 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
  3. 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 dosing details in manuscript have been reviewed by our editors PubMed
  4. NSABP C-04: Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, Bear HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999 Nov;17(11):3553-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00425152
    1. Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article PubMed
  5. 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 dosing details in manuscript have been reviewed by our editors PubMed
  6. 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
  7. 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 dosing details in manuscript have been reviewed by our editors PubMed
  8. 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 dosing details in manuscript have been reviewed by our editors 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
  9. 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; ABCSG. 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 dosing details in manuscript have been reviewed by our editors PubMed
  10. 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 dosing details in manuscript have been reviewed by our editors PubMed


FULV & Levamisole

FULV & Levamisole: 5-FU, LeucoVorin, Levamisole

Regimen variant #1, 5-FU 370 x 6 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
O'Connell et al. 1998 Not reported Phase 3 (E-esc) 5-FU & Levamisole Superior OS

Preceding treatment

Chemotherapy

Immunotherapy

28-day cycle for 2 cycles, then 35-day cycle for 4 cycles


Regimen variant #2, 5-FU 425 x 6 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Poplin et al. 2005 (SWOG S9415) 1994-1999 Phase 3 (C) 5-FU & Levamisole; CIFU Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

Immunotherapy

  • Levamisole (Ergamisol) as follows:
    • Cycles 1 & 2: 50 mg PO three times per day on days 1 to 3, 15 to 17
    • Cycles 3 & 5: 50 mg PO three times per day on days 1 to 3, 15 to 17, 29 to 31
    • Cycles 4 & 6: 50 mg PO three times per day on days 8 to 10, 22 to 24

28-day cycle for 2 cycles, then 35-day cycle for 4 cycles


Regimen variant #3, 12 months

Study Dates of enrollment Evidence Comparator Comparative Efficacy
O'Connell et al. 1998 Not reported Phase 3 (E-esc) 5-FU & Levamisole Superior OS

Preceding treatment

Chemotherapy

Immunotherapy

28-day cycle for 2 cycles, then 35-day cycle for 10 cycles

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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00002593
  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-B

mFOLFOX6-B: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Allegra et al. 2009 (NSABP C-08) 2004-2006 Phase 3 (E-esc) mFOLFOX6 Did not meet primary endpoint of DFS1
DFS36: 77.9% vs 75.1%
(HR 0.93, 95% CI 0.81-1.08)

1Reported efficacy is based on the 2013 update.
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

Targeted therapy

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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00096278
    1. Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011 Jan 1;29(1):11-6. Epub 2010 Oct 12. link to original article link to PMC article PubMed
    2. Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Lopa SH, Wolmark N. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol. 2013 Jan 20;31(3):359-64. Epub 2012 Dec 10. link to original article link to PMC article PubMed


MOF

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Wolmark et al. 1988 (NSABP C-01) 1977-1983 Phase 3 (E-esc) 1. Observation
2. BCG
Did not meet co-primary endpoints of DFS/OS1
Wolmark et al. 1993 (NSABP C-03) 1987-1989 Phase 3 (C) FULV Inferior OS

1Reported efficacy for NSABP C-01 is based on the 2004 update.

Preceding treatment

Chemotherapy

10-week cycle for 8 cycles

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; NSABP. 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed