Colon cancer

Adjuvant therapy

5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV)

Regimen

• Folinic acid (Leucovorin) 20 mg/m2 IV push before 5-FU days 1-5
• Fluorouracil (5-FU) 425 mg/m2 IV push days 1-5

Two different schedules have been used:

1. Q4weeks x 3 cycles, then Q5weeks x 3 cycles
2. Q4weeks x 6 cycles

References

1. O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997 Jan;15(1):246-50. link to original article (contains protocol) PubMed
2. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article (contains protocol) PubMed
3. 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 protocol) PubMed
4. 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 protocol) PubMed

5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV)

Regimen

• Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours weekly x 6 weeks
• Fluorouracil (5-FU) 500 mg/m2 IV push 1 hour after start of leucovorin weekly x 6 weeks

Q8weeks x 4 cycles

References

1. 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 protocol) PubMed
2. 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 protocol) PubMed
3. 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 protocol) PubMed

Capecitabine (Xeloda)

Regimen

• Capecitabine (Xeloda) 1250 mg/m2 PO BID days 1-14

Q21days x 8 cycles

References

1. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article (contains protocol) PubMed

FLOX

Regimen

• Fluorouracil (5-FU) 500 mg/m2 IV bolus 1 hour after start of leucovorin weekly x 6 weeks
• Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours weekly x 6 weeks
• Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on weeks 1, 3, 5; given prior to 5-FU and leucovorin

Q8weeks x 3 cycles

References

1. 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 protocol) PubMed

FOLFOX 4

Regimen

• Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours; both bolus and continuous infusion given on days 1 & 2
• Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours before 5-FU on days 1 and 2
• Oxaliplatin (Eloxatin) 85 mg/m2 in 250 mL of 5% dextrose IV over 2 hours concurrent with leucovorin day 1

Q14days x 12 cycles

References

1. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. link to original article (contains protocol) PubMed
2. 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 protocol) PubMed
3. Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. link to original article PubMed
4. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article PubMed

modified FOLFOX 6

Regimen

• Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
• Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours day 1
• Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours day 1

Q14days x 12 cycles

References

1. Kojima S, Ina K, Futamura Y, Ito Y, Hibi S, Nagaoka M, Yuasa S, Kawai M, Nagao S, Kataoka T. A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer. Gan To Kagaku Ryoho. 2007 Feb;34(2):203-6.

link to original article (Japanese) PubMed

FULV

Regimen

• Fluorouracil (5-FU) 500 mg/m2 IV bolus 1 hour after start of leucovorin weekly x 6
• Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours weekly x 6

Q8weeks x 3 cycles

References

1. 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 protocol) PubMed

UFT & leucovorin

Regimen

• Uracil-tegafur (UFT) 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) x 4 weeks
• Folinic acid (Leucovorin) 30 mg PO Q8H (total dose of 90 mg/day) x 4 weeks
• No food for 1 hour before and after each dose of medication.

Q5weeks x 5 cycles

References

1. 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 protocol) PubMed

XELOX (CapeOx)

Regimen

• Capecitabine (Xeloda) 1000 mg/m2 PO BID days 1-14
• Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours day 1

Q21days x 8 cycles

References

1. Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article (contains protocol) PubMed
2. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article (contains protocol) PubMed