Rectal cancer

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Please be aware that some regimens listed here are studies for colon cancer. These regimens were listed as options by the NCCN, Rectal Cancer version 3.2012, and their inclusion here reflects the overlap between treatments of colon and rectal cancer.

Adjuvant chemotherapy

Capecitabine (Xeloda)

Regimen

Level of Evidence: Phase III

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

21-day cycles 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 verified protocol PubMed

CapeOx (XELOX)

CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin

Regimen

Level of Evidence: Phase III

• 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 day 1

21-day cycles 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 verified protocol PubMed

FLOX

FLOX: Fluorouracil, Leucovorin, OXaliplatin

Regimen

Level of Evidence: Phase III

• 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

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 verified protocol PubMed

Fluorouracil (5-FU) & Folinic acid (Leucovorin)

Regimen #1, simplified biweekly (sLV5FU2), André, et al. 1999

Level of Evidence: Phase II

Note: The reference cited by the NCCN, Rectal Cancer version 3.2012, is for patients with metastatic disease. No primary reference for adjuvant use of these dosages could be found.

• Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours day 1 (administer first)
• Fluorouracil (5-FU) 400 mg/m2 IV bolus after leucovorin, then 1200 mg/m2/day IV continuous infusion over 46-48 hours

14-day cycles x 12 cycles

Regimen #2, Van Cutsem, et al. 2009 (PETACC-3) & Baumgaertner, et al. 2010 (GERCOR C96.1)

Level of Evidence: Phase III

• 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

14-day cycles x 12 cycles

Regimen #3, 5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV); Haller, et al. 2005; Lembersky, et al. 2006; Schmoll, et al. 2007

Level of Evidence: Phase III

Note: The Petrelli, et al. 1989 reference cited by the NCCN, Rectal Cancer version 3.2012, is for patients with metastatic disease, and the regimen differs from what is listed by the NCCN. The other references contain the correct regimen. The NCCN lists a 6-month course of therapy, whereas the other references list either a 6 to 8-month course of therapy.

• 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

8-week cycles x 3-4 cycles

References

1. Petrelli N, Douglass HO Jr, Herrera L, Russell D, Stablein DM, Bruckner HW, Mayer RJ, Schinella R, Green MD, Muggia FM, et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group. J Clin Oncol. 1989 Oct;7(10):1419-26. link to original article PubMed
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, André T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. Epub 2009 May 18. link to original article contains verified protocol PubMed
9. Baumgaertner I, Quinaux E, Khalil A, Louvet C, Buyse M, de Gramont A, André T; GERCOR Group. Comparison of the levogyre and dextro-levogyre forms of leucovorin in a phase III trial of bimonthly LV5FU2 versus monthly 5-fluorouracil and high-dose leucovorin for patients with stage II and III colon cancer (GERCOR C96.1). Clin Colorectal Cancer. 2010 Apr;9(2):E5-10. link to original article contains protocol PubMed

Fluorouracil, Folinic acid, Levamisole

Regimen, Haller, et al. 2005 (Intergroup 0089)

Level of Evidence: Phase III

Not in routine use; used as a comparator arm and here for reference purposes only.

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

28-day cycles x 3 cycles, then 35-day cycles x 3 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 verified protocol PubMed

mFOLFOX 6

Regimen

Level of Evidence: Phase III

• 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

14-day cycles 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
2. 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

Adjuvant chemoradiation

Capecitabine (Xeloda)

Regimen

Level of Evidence: Phase III

Prior to chemoradiation:

• Capecitabine (Xeloda) 1250 mg/m2 PO BID (2500 mg/m2/day) on days 1 to 14

21-day cycles x 2 cycles

Chemoradiation:

• Capecitabine (Xeloda) 825 mg/m2 PO BID (1650 mg/m2/day) on days 1 to 38
• Concurrent radiation therapy, 50.4 Gy total

After chemoradiation:

• Capecitabine (Xeloda) 1250 mg/m2 PO BID (2500 mg/m2/day) on days 1 to 14

21-day cycles x 3 cycles

References

1. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Apr 12. [Epub ahead of print] link to original article contains verified protocol PubMed

Fluorouracil (5-FU) & RT

Regimen #1, Smalley, et al. 2006

Level of Evidence: Phase III

Prior to chemoradiation:

• Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles

Chemoradiation starting on day 57:

• Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion while radiation is being given
• Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions for an initial dose of 45 Gy, which is followed by a 1.8 Gy x 3 fraction (5.4 Gy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 1.8 Gy x 2 fraction (3.6 Gy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided

After chemoradiation:

• Fluorouracil (5-FU) 450 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles, to start 28 days after completion of chemoradiation

Regimen #2, Hofheinz, et al. 2012

Level of Evidence: Phase III

Prior to chemoradiation:

• Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles

Chemoradiation:

• Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion while radiation is being given
• Concurrent radiation therapy, 50.4 Gy total

After chemoradiation:

• Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles

Regimen #3, Smalley, et al. 2006

Level of Evidence: Phase III

Prior to chemoradiation:

• Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion on days 1 to 42

8-week course (2 weeks off of chemotherapy prior to chemoradiation)

Chemoradiation starting on day 57:

• Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion while radiation is being given
• Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions for an initial dose of 45 Gy, which is followed by a 1.8 Gy x 3 fraction (5.4 Gy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 1.8 Gy x 2 fraction (3.6 Gy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided

After chemoradiation:

• Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion on days 1 to 56

56-day course, to start 28 days after completion of chemoradiation

Regimen #4, Tepper, et al. 1997 & Tepper, et al. 2002

Level of Evidence: Phase III

Prior to chemoradiation:

• Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles

Chemoradiation:

• Fluorouracil (5-FU) 500 mg/m2 IV bolus 3 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
• Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions for an initial dose of 45 Gy, which is followed by a 1.8 Gy x 3 fraction (5.4 Gy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 1.8 Gy x 2 fraction (3.6 Gy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided

After chemoradiation:

• Fluorouracil (5-FU) 450 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles, to start 28 days after completion of chemoradiation

Regimen #5

Level of Evidence: Non-randomized

Note: The O'Connell, et al. 1994 reference cited by the NCCN, Rectal Cancer version 3.2012, contains a different regimen than what is listed by the NCCN. No primary reference could be found for this exact regimen as listed by the NCCN.

• Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion either 5 or 7 days per week during radiation therapy

References

1. O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. link to original article PubMed
2. Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article contains verified protocol PubMed
3. Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article contains verified protocol PubMed
4. Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, Fisher B, Rich TA, Martenson JA, Kugler JW, Benson AB 3rd, Haller DG, Mayer RJ, Atkins JN, Cripps C, Pedersen J, Periman PO, Tanaka MS Jr, Leichman CG, Macdonald JS. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006 Aug 1;24(22):3542-7. link to original article contains verified protocol PubMed
5. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Apr 12. [Epub ahead of print] link to original article contains verified protocol PubMed

Fluorouracil (5-FU), Folinic acid (Leucovorin), RT

Regimen

Level of Evidence: Phase III

Prior to chemoradiation:

• Fluorouracil (5-FU) 425 mg/m2 IV bolus on days 1 to 5, given after Folinic acid (Leucovorin)
• Folinic acid (Leucovorin) 20 mg/m2 IV bolus on days 1 to 5, given before Fluorouracil (5-FU)

28-day cycles x 2 cycles

Chemoradiation:

• Fluorouracil (5-FU) 400 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
• Folinic acid (Leucovorin) 20 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
• Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions for an initial dose of 45 Gy, which is followed by a 1.8 Gy x 3 fraction (5.4 Gy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 1.8 Gy x 2 fraction (3.6 Gy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided

After chemoradiation:

• Fluorouracil (5-FU) 380 mg/m2 IV bolus on days 1 to 5
• Folinic acid (Leucovorin) 20 mg/m2 IV bolus on days 1 to 5

28-day cycles x 2 cycles, to start 28 days after completion of chemoradiation

References

1. Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article contains verified protocol PubMed
2. Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article contains verified protocol PubMed

Advanced or metastatic disease

See Colon cancer - Advanced or metastatic disease. The regimens listed by the NCCN, Rectal Cancer version 3.2012, are identical to the list for Colon Cancer version 2.2012, with the same references.