Difference between revisions of "Colon cancer"
(updates to FOLFIRI & Cetuximab (Erbitux)) |
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==FOLFIRI== | ==FOLFIRI== | ||
FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | ||
+ | |||
===Regimen=== | ===Regimen=== | ||
*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours on day 1, given during irinotecan infusion | *[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours on day 1, given during irinotecan infusion | ||
− | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours on days 1-2, given last | + | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last |
**In André, et al. 1999, the continuous infusion dose of Fluorouracil (5-FU) could be increased from 1200 mg/m2/day to 1500 mg/m2/day if there were no toxicities higher than grade 1 | **In André, et al. 1999, the continuous infusion dose of Fluorouracil (5-FU) could be increased from 1200 mg/m2/day to 1500 mg/m2/day if there were no toxicities higher than grade 1 | ||
*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first together with leucovorin | *[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first together with leucovorin | ||
Line 337: | Line 338: | ||
==FOLFIRI & Bevacizumab (Avastin)== | ==FOLFIRI & Bevacizumab (Avastin)== | ||
+ | FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | ||
+ | |||
===Regimen=== | ===Regimen=== | ||
− | |||
*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | *[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last | ||
*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first | *[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first | ||
*[[Bevacizumab (Avastin)]] 5 mg/kg IV on day 1 | *[[Bevacizumab (Avastin)]] 5 mg/kg IV on day 1 | ||
Line 350: | Line 353: | ||
==FOLFIRI & Cetuximab (Erbitux)== | ==FOLFIRI & Cetuximab (Erbitux)== | ||
+ | FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | ||
+ | |||
===Regimen=== | ===Regimen=== | ||
− | |||
*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | *[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | ||
**[[Levoleucovorin (Fusilev)]] 200 mg/m2 IV over 2 hours on day 1 can be used instead of [[Folinic acid (Leucovorin)]] | **[[Levoleucovorin (Fusilev)]] 200 mg/m2 IV over 2 hours on day 1 can be used instead of [[Folinic acid (Leucovorin)]] | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 hours on days 1-2, given last | ||
*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given 1 hour after completion of cetuximab | *[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given 1 hour after completion of cetuximab | ||
*[[Cetuximab (Erbitux)]] 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, [[Cetuximab (Erbitux)]] is 250 mg/m2 IV over 60 minutes on days 1 & 8; cetuximab is given first and infusion is to finish 1 hour before FOLFIRI begins | *[[Cetuximab (Erbitux)]] 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, [[Cetuximab (Erbitux)]] is 250 mg/m2 IV over 60 minutes on days 1 & 8; cetuximab is given first and infusion is to finish 1 hour before FOLFIRI begins | ||
Line 366: | Line 371: | ||
==FOLFIRI & Panitumumab (Vectibix)== | ==FOLFIRI & Panitumumab (Vectibix)== | ||
+ | FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | ||
===Regimen=== | ===Regimen=== | ||
− | |||
*[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | *[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last | ||
*[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first | *[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given first | ||
*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes day 1 | *[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes day 1 | ||
Line 376: | Line 382: | ||
===References=== | ===References=== | ||
# Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. [http://jco.ascopubs.org/content/28/31/4706.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20921462 PubMed] | # Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. [http://jco.ascopubs.org/content/28/31/4706.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20921462 PubMed] | ||
+ | |||
+ | ==FOLFIRI & Ziv-aflibercept (Zaltrap)== | ||
+ | FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | ||
+ | ===Regimen=== | ||
+ | ''This regimen is listed based on the abstract & package insert cited below, which did not specifically describe how FOLFIRI was given. No peer-reviewed journal reference is available at this time.'' | ||
+ | *[[Folinic acid (Leucovorin)]] 400 mg/m2 IV over 2 hours on day 1, given during irinotecan infusion | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last | ||
+ | *[[Irinotecan (Camptosar)]] 180 mg/m2 IV over 30-90 minutes on day 1, given together with leucovorin | ||
+ | *[[Ziv-aflibercept (Zaltrap)]] 4 mg/kg IV over 1 hour on day 1 | ||
+ | |||
+ | '''14-day cycles, given until progression of disease or unacceptable toxicity''' | ||
+ | |||
+ | ===References=== | ||
+ | # J. Tabernero, E. Van Cutsem, R. Lakomy, J. Prausova, P. Ruff, G. Van Hazel, V. Moiseyenko, D. Ferry, J. McKendrick, K. Soussan-Lazard, E. Boelle, C. Allegra. VELOUR, a Phase 3 Study of Aflibercept (A) Versus Placebo (pbo) in Combination with FOLFIRI for the Treatment of Patients (pt) with Previously Treated Metastatic Colorectal Cancer (MCRC). [http://stockholm2011.ecco-org.eu/Programme.aspx 2011 European Multidisciplinary Congress]. Abstract 6LBA. Presented September 25, 2011. [http://new.ecco-org.eu/ecco_content/2011StockholmLateBreakingflipbook/files/assets/seo/page9.html link to abstract] | ||
+ | # [http://www.regeneron.com/zaltrap/zaltrap-fpi.pdf Ziv-aflibercept (Zaltrap) package insert] | ||
==FOLFOX 4== | ==FOLFOX 4== |
Revision as of 23:28, 3 August 2012
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Adjuvant therapy
Capecitabine (Xeloda)
Regimen
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1-14
21-day cycles x 8 cycles
References
- 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 verified protocol PubMed
CapeOx (XELOX)
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin
Regimen #1, Schmoll, et al. 2007
Note: This is the same trial as described by Haller, et al. 2011, but the schedule for Capecitabine (Xeloda) is slightly different.
- Capecitabine (Xeloda) 1000 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours on day 1
21-day cycles x 8 cycles
Regimen #2, Haller, et al. 2011
Note: This is the same trial as described by Schmoll, et al. 2007, but the schedule for Capecitabine (Xeloda) is slightly different.
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1-14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours on day 1
21-day cycles x 8 cycles
References
- 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 verified protocol PubMed
- 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 verified protocol PubMed
Fluorouracil (5-FU) & Folinic acid (Leucovorin)
Regimen #1, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), O'Connell, et al. 1997 & Haller, et al. 2005
- Folinic acid (Leucovorin) 20 mg/m2 IV push before 5-FU on days 1-5
- Fluorouracil (5-FU) 425 mg/m2 IV push on days 1-5
28-day cycles x 3 cycles, then 35-day cycles x 3 cycles
Regimen #2, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), Twelves, et al. 2005 & Schmoll, et al. 2007
- Folinic acid (Leucovorin) 20 mg/m2 IV push before 5-FU on days 1-5
- Fluorouracil (5-FU) 425 mg/m2 IV push on days 1-5
28-day cycles x 6 cycles
Regimen #3, 5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV); Haller, et al. 2005; Lembersky, et al. 2006; Schmoll, et al. 2007; Kuebler, et al. 2007
- Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours on days 1, 8, 15, 22, 29, 36, given first
- Fluorouracil (5-FU) 500 mg/m2 IV push on days 1, 8, 15, 22, 29, 36, 1 hour after start of leucovorin
8-week cycles x 3-4 cycles
References
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article contains verified protocol PubMed
- 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
FLOX
FLOX: Fluorouracil, Leucovorin, OXaliplatin
Regimen
- Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1, 8, 15, 22, 29, 36, to start 1 hour after start of leucovorin
- Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours on days 1, 8, 15, 22, 29, 36, given before Fluorouracil (5-FU)
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on days 1, 15, 29, given prior to 5-FU and leucovorin
8-week cycles x 3 cycles
References
- Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. link to original article contains verified protocol PubMed
FOLFOX 4
Also known as FOLFOX4.
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 & 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours concurrent with leucovorin on day 1
14-day cycles x 12 cycles
References
- de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. link to original article contains verified protocol--regimen was not used in adjuvant setting PubMed
- André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. link to original article contains verified protocol PubMed
- Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. link to original article PubMed
- Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article regimen was not used in adjuvant setting PubMed
mFOLFOX 6
Regimen
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
14-day cycles x 12 cycles, to start within 10 weeks of surgery
References
- 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 PubMed
- Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012 Apr 4;307(13):1383-93. link to original article contains verified protocol PubMed
UFT & leucovorin
Regimen
- Uracil-tegafur (UFT) 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) on days 1-28
- Folinic acid (Leucovorin) 30 mg PO Q8H (total dose of 90 mg/day) on days 1-28
- No food for 1 hour before and after each dose of medication.
35-day cycles x 5 cycles
References
- 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 verified protocol PubMed
Advanced or metastatic disease
Capecitabine (Xeloda)
Regimen
Note: The NCCN, Colon Cancer version 2.2012, lists Capecitabine (Xeloda) 850-1250 mg/m2 as the dosage range. No primary reference for the lower monotherapy dosages could be found.
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1-14
21-day cycles
References
- Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol PubMed
- Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol PubMed
Capecitabine (Xeloda) & Bevacizumab (Avastin)
Regimen
Note: The NCCN, Colon Cancer version 2.2012, lists Capecitabine (Xeloda) 850-1250 mg/m2 as the dosage range.
- Capecitabine (Xeloda) 650-1250 mg/m2 PO BID on days 1-14
- Bevacizumab (Avastin) 7.5 mg/kg IV on day 1
21-day cycles
References
- Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol--this regimen did not include bevacizumab PubMed
- Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol--this regimen did not include bevacizumab PubMed
- Moehler M, Sprinzl MF, Abdelfattah M, Schimanski CC, Adami B, Godderz W, Majer K, Flieger D, Teufel A, Siebler J, Hoehler T, Galle PR, Kanzler S. Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients. World J Gastroenterol. 2009 Jan 28;15(4):449-56. link to original article contains verified protocol--this regimen also included treatment with irinotecan PubMed
- Pietrantonio F, Biondani P, Pellegrinelli A, Marchianò A, Dotti KF, Buzzoni R, Bartolomeo MD. Hepatic colorectal cancer metastases showing a distinctive pattern of pathological response after metronomic capecitabine and bevacizumab. Med Oncol. 2012 Jan 21. [Epub ahead of print] link to original article contains verified protocol PubMed
CapeOx (XELOX)
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin
Regimen
- Capecitabine (Xeloda) 850-1000 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours on day 1
21-day cycles
References
- 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 verified protocol PubMed
- Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed
CapeOx (XELOX) & Bevacizumab (Avastin)
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin
Regimen
- Capecitabine (Xeloda) 850-1000 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours on day 1
- Bevacizumab (Avastin) 7.5 mg/kg IV over 15 minutes on day 1
21-day cycles
References
- 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 verified protocol PubMed
- Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed
Cetuximab (Erbitux)
Regimen #1, Cunningham, et al. 2004; Lenz, et al. 2006; Jonker, et al. 2007; Asmis, et al. 2011
- Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes on days 1 & 8
14-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications (varies depending on reference):
- Antihistamine (such as Diphenhydramine (Benadryl) 50 mg IV) prior to at least the first infusion cetuximab
Regimen #2, Martín-Martorell, et al. 2008
Note: The NCCN, Colon Cancer version 2.2012, lists this dosage and schedule as an option, although no primary reference could be found for this exact regimen. The regimen described by Martín-Martorell, et al. 2008 used cetuximab together with irinotecan.
- Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours on day 1
- If tolerated, subsequent doses of cetuximab can be given over 1 hour
14-day cycles
Supportive medications:
- Antihistamine prior to cetuximab
References
- Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article contains verified protocol PubMed
- Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006 Oct 20;24(30):4914-21. link to original article contains verified protocol PubMed
- Bristol-Myers Squibb and ImClone. A Phase III Randomized Study of Cetuximab (Erbitux, C225) and Best Supportive Care Versus Best Supportive Care in Patients with Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma. Final Clinical Study Report for CA225025. 2007 Mar 5. link to original report contains verified protocol
- Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. link to original article contains verified protocol PubMed
- Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. link to original article contains verified protocol--see note above PubMed
- Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-26. Epub 2010 Jul 5. link to original article contains verified protocol PubMed
Cetuximab (Erbitux) & Irinotecan (Camptosar)
Regimen #1, Cunningham, et al. 2004 & Sobrero, et al. 2008
- Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days 8 & 15 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes on days 1, 8, 15
- Irinotecan (Camptosar) 350 mg/m2 IV over 90 minutes on day 1
- If aged 70 years old or more, ECOG performance status 2 or more, or prior pelvic radiation, Irinotecan (Camptosar) is 300 mg/m2 IV over 90 minutes on day 1
21-day cycles
Supportive medications:
- Antihistamine prior to at least the first infusion of cetuximab
Regimen #2, Cunningham, et al. 2004
- Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days 8, 15, 22, 29, 36 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes on days 1, 8, 15, 22
42-day cycles
Supportive medications:
- Antihistamine prior to at least the first infusion cetuximab
Regimen #3
Note: In contrast to Cunningham, et al. 2004, the NCCN, Colon Cancer version 2.2012, lists Irinotecan (Camptosar) as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this.
- Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days 8 & 15 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes on days 1, 8, 15
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes on days 1 & 8
21-day cycles
Supportive medications:
- Antihistamine prior to at least the first infusion cetuximab
Regimen #4, Martín-Martorell, et al. 2008
- Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours on day 1
- If tolerated, subsequent doses of cetuximab can be given over 1 hour
- Irinotecan (Camptosar) 180 mg/m2 IV over 30 minutes on day 1
14-day cycles
Supportive medications:
- Antihistamine prior to cetuximab
- Dexamethasone & ondansetron prior to irinotecan
References
- Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article contains verified protocol PubMed
- Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. Epub 2008 Apr 7. link to original article contains verified protocol PubMed
- Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. link to original article contains verified protocol PubMed
Fluorouracil (5-FU) & Folinic acid (Leucovorin)
Regimen #1, de Gramont, et al. 2000
- Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours on days 1 & 2, given first before 5-FU
- 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
14-day cycles
Regimen #2, modified de Gramont, Cheeseman, et al. 2002
- Folinic acid (Leucovorin) 350 mg IV over 2 hours on day 1, given first
- Instead of Folinic acid (Leucovorin), an alternative is Levoleucovorin (Fusilev) 175 mg IV over 2 hours on day 1, given first
- Fluorouracil (5-FU) 400 mg/m2 IV bolus over 5 minutes on day 1 after leucovorin, then 1400 mg/m2/day (total dose of 2800 mg/m2) IV continuous infusion over 46 hours on days 1-2
14-day cycles
Supportive medications:
- No routine prophylactic antiemetics and antidiarrheal medications were used, but patients could use metoclopramide (Reglan) prn nausea and loperamide (Imodium) prn diarrhea.
Regimen #3, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), Hoff, et al. 2001 & Van Cutsem, et al. 2001
- Folinic acid (Leucovorin) 20 mg/m2 IV push before 5-FU on days 1-5
- Fluorouracil (5-FU) 425 mg/m2 IV push on days 1-5
28-day cycles
- Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours on days 1, 8, 15, 22, 29, 36
- Fluorouracil (5-FU) 500 mg/m2 IV push on days 1, 8, 15, 22, 29, 36, 1 hour after start of leucovorin
8-week cycles
Regimen #5, Jäger, et al. 1996
- Folinic acid (Leucovorin) 20 mg/m2 IV over 2 hours on day 1, given first
- Fluorouracil (5-FU) 500 mg/m2 IV bolus on day 1, 1 hour after start of leucovorin
7-day cycles
Regimen #6, simplified biweekly (sLV5FU2), André, et al. 1999
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1, given first
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1 after leucovorin, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2
14-day cycles
Regimen #7, Douillard, et al. 2000
- Folinic acid (Leucovorin) 500 mg/m2 IV on day 1
- Fluorouracil (5-FU) 2600 mg/m2 IV over 24 hours on day 1
7-day cycles
References
- Jäger E, Heike M, Bernhard H, Klein O, Bernhard G, Lautz D, Michaelis J, Meyer zum Büschenfelde KH, Knuth A. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol. 1996 Aug;14(8):2274-9. link to original article contains verified protocol PubMed
- André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. link to original article contains verified protocol PubMed
- Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000 Mar 25;355(9209):1041-7. link to original article contains verified protocol PubMed
- 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 verified protocol PubMed
- Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol PubMed
- Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol PubMed
- Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002 Aug 12;87(4):393-9. link to original article contains verified protocol PubMed
- Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003 Jan 1;21(1):60-5. link to original article contains verified protocol PubMed
FOLFIRI
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1, given during irinotecan infusion
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last
- In André, et al. 1999, the continuous infusion dose of Fluorouracil (5-FU) could be increased from 1200 mg/m2/day to 1500 mg/m2/day if there were no toxicities higher than grade 1
- Irinotecan (Camptosar) 180 mg/m2 IV over 30-90 minutes on day 1, given first together with leucovorin
14-day cycles
References
- André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. link to original article contains verified protocol PubMed
- Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. link to original article contains verified protocol PubMed
- Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol. 2008 Feb 1;26(4):689-90. link to original article PubMed
- Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article contains verified protocol PubMed
FOLFIRI & Bevacizumab (Avastin)
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last
- Irinotecan (Camptosar) 180 mg/m2 IV over 30-90 minutes on day 1, given first
- Bevacizumab (Avastin) 5 mg/kg IV on day 1
14-day cycles
References
- Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. link to original article contains verified protocol PubMed
- Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol. 2008 Feb 1;26(4):689-90. link to original article PubMed
FOLFIRI & Cetuximab (Erbitux)
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1
- Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours on day 1 can be used instead of Folinic acid (Leucovorin)
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 hours on days 1-2, given last
- Irinotecan (Camptosar) 180 mg/m2 IV over 30-90 minutes on day 1, given 1 hour after completion of cetuximab
- Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) is 250 mg/m2 IV over 60 minutes on days 1 & 8; cetuximab is given first and infusion is to finish 1 hour before FOLFIRI begins
14-day cycles, given until progression of disease or unacceptable toxicity
References
- Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. link to original article contains verified protocol PubMed
- E. Van Cutsem, I. Lang, G. Folprecht, M. Nowacki, C. Barone, I. Shchepotin, J. Maurel, D. Cunningham, I. Celik, C. Kohne. Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome. 2010 ASCO Annual Meeting abstract 3570. link to abstract
- Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
- Bokemeyer C, Cutsem EV, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article PubMed
FOLFIRI & Panitumumab (Vectibix)
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours, started during irinotecan infusion on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last
- Irinotecan (Camptosar) 180 mg/m2 IV over 30-90 minutes on day 1, given first
- Panitumumab (Vectibix) 6 mg/kg IV over 60 minutes day 1
14-day cycles
References
- Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article contains verified protocol PubMed
FOLFIRI & Ziv-aflibercept (Zaltrap)
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen
This regimen is listed based on the abstract & package insert cited below, which did not specifically describe how FOLFIRI was given. No peer-reviewed journal reference is available at this time.
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1, given during irinotecan infusion
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2, given last
- Irinotecan (Camptosar) 180 mg/m2 IV over 30-90 minutes on day 1, given together with leucovorin
- Ziv-aflibercept (Zaltrap) 4 mg/kg IV over 1 hour on day 1
14-day cycles, given until progression of disease or unacceptable toxicity
References
- J. Tabernero, E. Van Cutsem, R. Lakomy, J. Prausova, P. Ruff, G. Van Hazel, V. Moiseyenko, D. Ferry, J. McKendrick, K. Soussan-Lazard, E. Boelle, C. Allegra. VELOUR, a Phase 3 Study of Aflibercept (A) Versus Placebo (pbo) in Combination with FOLFIRI for the Treatment of Patients (pt) with Previously Treated Metastatic Colorectal Cancer (MCRC). 2011 European Multidisciplinary Congress. Abstract 6LBA. Presented September 25, 2011. link to abstract
- Ziv-aflibercept (Zaltrap) package insert
FOLFOX 4
Also known as FOLFOX4.
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 & 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours concurrent with leucovorin on day 1
14-day cycles
References
- de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. link to original article contains verified protocol PubMed
- Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. link to original article PubMed content property of HemOnc.org
- 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
mFOLFOX 6
Regimen #1, Cheeseman, et al. 2002 & Hochster, et al. 2008
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 hours on days 1-2
- Folinic acid (Leucovorin) 350 mg/m2 IV over 2 hours on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
14-day cycles
Regimen #2, Boccia, et al. 2010 & Saltz, et al. 2011
Note: Neither of the references cited by the NCCN, Colon Cancer version 2.2012, contained this 400 mg/m2 dosage of leucovorin. The two references listed here contain the 400 mg/m2 dosage, but mFOLFOX 6 is in combination with cetuximab and/or bevacizumab. No primary reference for this dosage of mFOLFOX 6 by itself could be found.
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46-48 hours on days 1-2
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
14-day cycles
References
- Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002 Aug 12;87(4):393-9. link to original article contains verified protocol PubMed
- Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed
- Boccia RV, Cosgriff TM, Headley DL, Badarinath S, Dakhil SR. A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2010 Apr;9(2):102-7. link to original article contains protocol PubMed
- Saltz L, Badarinath S, Dakhil S, Bienvenu B, Harker WG, Birchfield G, Tokaz LK, Barrera D, Conkling PR, O'Rourke MA, Richards DA, Reidy D, Solit D, Vakiani E, Capanu M, Scales A, Zhan F, Boehm KA, Asmar L, Cohn A. Phase III Trial of Cetuximab, Bevacizumab, and 5-Fluorouracil/Leucovorin vs. FOLFOX-Bevacizumab in Colorectal Cancer. Clin Colorectal Cancer. 2011 Nov 4. [Epub ahead of print] link to original article contains protocol PubMed
FOLFOX & Bevacizumab (Avastin)
Regimen #1, mFOLFOX 6 & Bevacizumab (Avastin), Saltz, et al. 2011
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours on days 1-2
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
- Bevacizumab (Avastin) 5 mg/kg IV on day 1
14-day cycles
Regimen #2, FOLFOX 4 & Bevacizumab (Avastin), Emmanouilides, et al. 2007
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, 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 on days 1 & 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
- Bevacizumab (Avastin) 5 mg/kg IV on day 1, given first
- Infusion times for bevacizumab are 2 hours for cycle 1, 1 hour for cycle 2, then 30 minutes for cycles 3 and later
14-day cycles
References
- Emmanouilides C, Sfakiotaki G, Androulakis N, Kalbakis K, Christophylakis C, Kalykaki A, Vamvakas L, Kotsakis A, Agelaki S, Diamandidou E, Touroutoglou N, Chatzidakis A, Georgoulias V, Mavroudis D, Souglakos J. Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer. 2007 May 30;7:91. link to original article PubMed
- Saltz L, Badarinath S, Dakhil S, Bienvenu B, Harker WG, Birchfield G, Tokaz LK, Barrera D, Conkling PR, O'Rourke MA, Richards DA, Reidy D, Solit D, Vakiani E, Capanu M, Scales A, Zhan F, Boehm KA, Asmar L, Cohn A. Phase III Trial of Cetuximab, Bevacizumab, and 5-Fluorouracil/Leucovorin vs. FOLFOX-Bevacizumab in Colorectal Cancer. Clin Colorectal Cancer. 2011 Nov 4. [Epub ahead of print] link to original article contains protocol PubMed
FOLFOX & Panitumumab (Vectibix)
Regimen #1, FOLFOX 4 & Panitumumab (Vectibix), Douillard, et al. 2010
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, 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 on days 1 & 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
- Panitumumab (Vectibix) 6 mg/kg IV on day 1, given first
- Infusion times for panitumumab are 1 hour for cycle 1, then if tolerated, 30 minutes for cycle 2 and later
Regimen #2, mFOLFOX 6 & Panitumumab (Vectibix)
Note: The two references cited by the NCCN, Colon Cancer version 2.2012, contained different regimens. No primary reference for this regimen could be found.
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day IV continuous infusion over 46-48 hours on days 1-2
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1
- Panitumumab (Vectibix) 6 mg/kg IV over 60 minutes on day 1
14-day cycles
References
- Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, B?asin'ska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. link to original article PubMed
FOLFOXIRI
FOLFOXIRI: FOLinic acid, Fluorouracil, OXaliplatin, IRInotecan
Regimen
Note: In contrast to Falcone, et al. 2007, the NCCN, Colon Cancer version 2.2012, listed the dose of Folinic acid (Leucovorin) as 400 mg/m2 IV on day 1. No primary reference could be found for this.
- Fluorouracil (5-FU) 1600 mg/m2/day (3200 mg/m2 total dose) IV continuous infusion over 48 hours on days 1-2
- Folinic acid (Leucovorin) 200 mg/m2 IV on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV on day 1
- Irinotecan (Camptosar) 165 mg/m2 IV on day 1
14-day cycles
References
- Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. link to original article contains verified protocol PubMed
Irinotecan (Camptosar)
Regimen #1, Cunningham, et al. 1998 & Fuchs, et al. 2003
- Irinotecan (Camptosar) 350 mg/m2 IV over 90 minutes on day 1
- If aged 70 years old or more, ECOG performance status 2 or more, or prior pelvic radiation, Irinotecan (Camptosar) is 300 mg/m2 IV over 90 minutes on day 1
21-day cycles
Supportive medications (varied depending on reference):
- "Standard regimens of antiemetics, atropine, and intensive loperamide," but no prophylactic atropine allowed on cycle 1 day 1
Regimen #2, weekly irinotecan, Fuchs, et al. 2003
Note: In contrast to Fuchs, et al. 2003, the NCCN, Colon Cancer version 2.2012, listed Irinotecan (Camptosar) as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this.
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes on days 1, 8, 15, 22
42-day cycles
References
- Cunningham D, Pyrhönen S, James RD, Punt CJ, Hickish TF, Heikkila R, Johannesen TB, Starkhammar H, Topham CA, Awad L, Jacques C, Herait P. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1413-8. link to original article contains verified protocol PubMed
- Fuchs CS, Moore MR, Harker G, Villa L, Rinaldi D, Hecht JR. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol. 2003 Mar 1;21(5):807-14. link to original article contains verified protocol PubMed
IROX
IROX: IRinotecan, OXaliplatin
Regimen
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1, given first
- Irinotecan (Camptosar) 200 mg/m2 IV over 30-90 minutes on day 1, given second
21-day cycles
References
- Haller DG, Rothenberg ML, Wong AO, Koralewski PM, Miller WH Jr, Bodoky G, Habboubi N, Garay C, Olivatto LO. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol. 2008 Oct 1;26(28):4544-50. link to original article contains verified protocol PubMed
Panitumumab (Vectibix)
Regimen
- Panitumumab (Vectibix) 6 mg/kg IV over 60 minutes on day 1
14-day cycles, given until progression of disease or unacceptable toxicity
References
- Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. link to original article contains verified protocol PubMed