Colon Cancer Treatment Regimens

Colon Cancer Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategi es.

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These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Systemic Therapy for Advanced or Metastatic Disease1,a

REGIMEN

DOSING

Capecitabine2-5

Days 1–14: Capecitabine 1,000–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

Capecitabine + Bevacizumab2,6-8,b

Day 1: Bevacizumab 7.5mg/kg IV

Days 1–14: Capecitabine 850–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

CapeOX2,9-12,c

Days 1–15: Capecitabine 1,000mg/m2 orally twice daily (beginning in the evening of Day 1 and ending the morning of Day 15)

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

CapeOX + Bevacizumab2,6,11,12,b,c

Day 1: Bevacizumab 7.5mg/kg IV, followed by:

Days 1–15: Capecitabine 1,000mg/m2 orally twice daily (beginning in the evening of Day 1 and ending the morning of Day 15)

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Cetuximab
(KRAS/NRAS/BRAF WT)13-17,d,e

Cetuximab requires premedicationd

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours, followed by:

Day 1 beginning Week 2: Cetuximab 250mg/m2 IV over 60 minutes.

Repeat cycle weekly.

OR

Day 1: Cetuximab 500mg/m2 IV.

Repeat cycle every 2 weeks.

Dostarlimab-gxly
(dMMR/MSI-H only)18,19,f,g

Day 1: Dostarlimab-gxly 500mg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 weeks, followed by:

Day 1: Dostarlimab-gxly 1000mg IV over 30 minutes.

Repeat cycle every 6 weeks.

Encorafenib + Cetuximab
(BRAF V600E mutation positive)13,20-22,d,e

Cetuximab requires premedicationd

Days 1–28: Encorafenib 300mg orally once daily

Repeat cycle every 4 weeks, concurrent with:

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours, followed by:

Day 1 beginning with Week 2: Cetuximab 250mg/m2 IV over 60 minutes.

Repeat cycle weekly.

OR

Days 1–28: Encorafenib 300mg orally once daily

Repeat cycle every 4 weeks, concurrent with:

Day 1 of Week 1: Cetuximab 500mg/m2 IV over 2 hours.

Repeat cycle every 2 weeks.

Encorafenib + Panitumumab
(BRAF V600E mutation positive)20-23,e

Days 1–28: Encorafenib 300mg orally once daily.

Repeat cycle every 4 weeks, concurrent with:

Day 1: Panitumumab 6mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

Entrectinib (NTRK gene fusion positive)24-26

Days 1-28: Entrectinb 600mg orally once daily.

Repeat cycle every 4 weeks.

Fam-Trastuzumab Deruxtecan nxki (HER2-amplified and RAS and BRAF WT)27,28

Day 1: Fam-trastuzumab deruxtecan-nxki 6.4mg/kg IV.

Repeat cycle every 3 weeks.

FOLFIRI29-33,h,i

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 30-90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRI + Bevacizumab6,29-31,33,34,b,h,i

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes

Day 1: Leucovorin 400mg/m2 IV infusion, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Day 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion

Day 1: Bevacizumab 5mg/kg IV.

Repeat cycle every 2 weeks.

FOLFIRI + Cetuximab

(KRAS/NRAS/BRAF WT)13,29-32,35,36,d,e,h,i

Cetuximab requires premedicationd

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours, followed by:

Day 1 beginning with Week 2: Cetuximab 250mg/m2 IV over 60 minutes.

Repeat cycle weekly, concurrent with:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 0-90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

OR

Day 1 of Week 1: Cetuximab 500mg/m2 IV over 2 hours, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 30-90 minutes, followed by:

Days 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRI + Panitumumab

(KRAS/NRAS/BRAF WT)23,29-32,37,e,h,i

Day 1: Panitumumab 6mg/kg IV over 60 minutes, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes with:

Day 1: Leucovorin 400mg/m2 IV infusion, followed by:

Days 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRI + Ramucirumab29-31,38,39,h-j

Ramucirumab requires premedicationi

Day 1: Ramucirumab 8mg/kg IV over 60 minutes, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes with:

Day 1: Leucovorin 400mg/m2 IV over 30-90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRI + Ziv-aflibercept29-31,40,41,h,i

Day 1: Ziv-aflibercept 4mg/kg IV over 1 hour

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes

Day 1: Leucovorin 400mg/m2 IV infusion

Days 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRINOX9,29-31,42,43,h,m-o

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 180mg/m2 IV over 30 to 90 minutes

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRINOX + Bevacizumab6,29-31,42,44,b,c,h,I,m-o

Day 1: Bevacizumab 5mg/kg IV, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 180mg/m2 IV over 30 to 90 minutes

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRINOX + Cetuximab

(KRAS/NRAS/BRAF WT)9,13,29-31,42,45,c,d,e,h,I,m-o

Cetuximab requires premedicationd

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours

Day 1 of Week 2: 250mg/m2 IV over 60 minutes, concurrent with:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 180mg/m2 IV over 30 to 90 minutes

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

OR

Day 1: Cetuximab 500mg/m2 IV over 2 hours, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 180mg/m2 IV over 30 to 90 minutes

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRINOX + Panitumumab (KRAS/NRAS/BRAF WT)9,23,29-31,45,46,c,e,h,I,m-o

Day 1: Panitumumab 6mg/kg IV over 60 minutes, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 180 mg/m2 IV over 30 to 90 minutes

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

Irinotecan31,47,48,i

Days 1 and 8: Irinotecan 125mg/m2 IV over 30–90 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Irinotecan 350mg/m2 IV over 30-90 minutes if age <70 years old

Day 1: Irinotecan 300mg/m2 IV over 30-90 minutes if age >70 years old, prior pelvic irradiation, or ECOG performance status >2.

Repeat cycle every 3 weeks.

OR

Day 1: Irinotecan 180mg/m2 IV over 30-90 minutes.

Repeat cycle every 2 weeks.

Irinotecan + Bevacizumab6,31,47,49,b,i

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes

Day 1: Bevacizumab 5mg/kg IV.

Repeat cycle every 2 weeks.

OR

Day 1: Irinotecan 350mg/m2 IV (age <70 years) over 30–90 minutes OR Irinotecan 300mg/m2 (age ≥70 years, prior pelvic irradiation, or ECOG performance status >2) over 30-90 minutes.

Day 1: Bevacizumab 7.5mg/kg IV.

Repeat cycle every 3 weeks.

Irinotecan + Cetuximab

(KRAS/NRAS/BRAF WT)13,14,31,33,36,50,d,e,i

Cetuximab requires premedicationd

Day 1 of Week 1: Cetuximab 400mg/m2 IV, followed by:

Day 1 beginning Week 2: Cetuximab 250mg/m2 IV.

Repeat cycle weekly, concurrent with:

Day 1: Irinotecan 350mg/m2 IV over 30-90 minutes if age <70 years old OR Irinotecan 300mg/m2 IV over 30-90 minutes if age >70 years old, prior pelvic irradiation, or ECOG performance status >2.

Repeat cycle every 3 weeks.

OR

Day 1: Cetuximab 500mg/m2 IV

Repeat cycle every 2 weeks, concurrent with:

Day 1: Irinotecan 350mg/m2 IV over 30-90 minutes if age <70 years old OR Irinotecan 300mg/m2 IV over 30-90 minutes if age >70 years old, prior pelvic irradiation, or ECOG performance status >2.

Repeat cycle every 3 weeks.

OR

Day 1 of Week 1: Cetuximab 400mg/m2 IV, followed by:

Day 1 beginning Week 2: Cetuximab 250mg/m2 IV

Repeat cycle weekly, concurrent with:

Day 1: Irinotecan 180mg/m2 IV over 30-90 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Cetuximab 500mg/m2 IV

Day 1: Irinotecan 180mg/m2 IV over 30-90 minutes.

Repeat cycle every 2 weeks.

OR

Day 1 of Week 1: Cetuximab 400mg/m2 IV, followed by:

Day 1 beginning Week 2: Cetuximab 250mg/m2 IV

Repeat cycle weekly, concurrent with:

Day 1,8: Irinotecan 125mg/m2 IV over 30-90 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Cetuximab 500mg/m2 IV, concurrent with:

Day 1,8: Irinotecan 125mg/m2 IV over 30-90 minute.s

Repeat cycle every 3 weeks.

Irinotecan + ­Panitumumab25,31,49,56,57,g,j (KRAS/NRAS/BRAF WT)23,31,37,51,52,e,i

Day 1: Panitumumab 6mg/kg IV over 60 minutes, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes.

Repeat cycle every 2 weeks

Irinotecan + Ramucirumab31,38,39,i,j

Ramucirumab requires premedicationj

Day 1: Ramucirumab 8mg/m2 over 60 minutes, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes.

Repeat cycle every 2 weeks.

Irinotecan + Ziv-aflibercept14,31,40,47,i

Day 1: Ziv-aflibercept 4mg/kg IV over 60 minutes, followed by:

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes.

Repeat cycle every 2 weeks

IROX9,31,53,c,i

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, followed by:

Day 1: Irinotecan 200mg/m2 over 30–90 minutes.

Repeat cycle every 3 weeks.

IROX + Bevacizumab6,9,31,53-55,b,c,i

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Irinotecan 200mg/m2 IV over 30–90 minutes

Day 1: Bevacizumab 7.5mg/kg IV.

Repeat cycle every 3 weeks.

Larotrectinib (NTRK gene fusion positive)56,57

Days 1-28: Larotrectinib 100mg orally twice daily.

Repeat cycle every 4 weeks.

mFOLFIRINOX9,29-31,42,43,c,h,I,l-n

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 150mg/m2 IV over 30 to 90 minutes, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFIRINOX + Bevacizumab6,9,29-31,42,43,b,c,h,k,I,l-n

Day 1: Bevacizumab 5mg/kg IV, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 150mg/m2 IV over 30 to 90 minutes, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFIRINOX + Cetuximab (KRAS/NRAS/BRAF WT)9,13,29-31,45,58,c-e,h,I-n

Day 1: Cetuximab 500mg/m2 IV, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 150mg/m2 IV over 30 to 90 minutes, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

OR

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours, followed by:

Day 1 of Week 2: Cetuximab 250mg/m2 IV over 60 minutes.

Repeat cycle weekly, concurrent with:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 150mg/m2 IV over 30 to 90 minutes, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFIRINOX + Panitumumab

(KRAS/NRAS/BRAF WT)9,13,29-31,45,46,58,c,e,h,I,l-n

Day 1: Panitumumab 6mg/kg IV over 60 minutes, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Irinotecan 150mg/m2 IV over 30 to 90 minutes, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX69,29,30,59-62,c,h,k,l

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX6 + Bevacizumab6,9,29,30,63-65,b,c,h,k,l

Day 1: Bevacizumab 5mg/kg IV, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX6 + Cetuximab

(KRAS/NRAS/BRAF WT)9,13,29,30,63,c-e,h,k,l

Day 1 of Week 1: Cetuximab 400mg/m2 IV over 2 hours, followed by:

Day 1 of Week 2: Cetuximab 250mg/m2 IV over 60 minutes.

Repeat cycle weekly, concurrent with:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

OR

Day 1: Cetuximab 500mg/m2 IV, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX6 + Panitumumab

(KRAS/NRAS/BRAF WT)9,23,29,30,60,65,66,c,e,h,k,l

Day 1: Panitumumab 6mg/kg IV over 60 minutes, followed by:

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX79,29,30,67,68,c,h,k,l

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours IV, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

Nivolumab

(dMMR/MSI-H only)69,70,f,g

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat every 2 weeks.

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Nivolumab + Ipilimumab

(dMMR/MSI-H only)69,71,72,f,g

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 3mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Panitumumab

(KRAS/NRAS/BRAF WT)23,73,e

Day 1: Panitumumab 6mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

Pembrolizumab

(dMMR/MSI-H only)74-76,f,g

Day 1: Pembrolizumab 200mg IV over 30 minutes

Repeat every 3 weeks for up to 2 years.

OR

Day 1: Pembrolizumab 2mg/kg IV over 30 minutes

Repeat cycle every 3 weeks for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat every 6 weeks for up to 2 years.

Regorafenib77-79,p

Days 1–7 of Cycle 1: Regorafenib 80mg orally once daily, followed by:

Days 8–14 of Cycle 1: Regorafenib 120mg orally once daily, followed by:

Days 15–21 of Cycle 1: Regorafenib 160mg orally once

Days 1–21 of Cycle 2: Regorafenib 160mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-21: Regorafenib 160mg orally once daily.

Repeat cycle every 4 weeks.

Roswell Park regimen Fluorouracil/Leucovorin29,30,80,81

Days 1,8,15,22,29, and 36: Leucovorin 500mg/m2 IV over 2 hours

Days 1,8,15,22,29, and 36: Fluorouracil 500mg/m2 IV push 1 hour after start of leucovorin.

Repeat cycle every 8 weeks (6 weeks on- followed by 2 weeks off-treatment).

Roswell Park regimen Fluorouracil/Leucovorin + Bevacizumab6,29,30,81,82,b

Days 1, 8, 15, 22, 29, and 36: Leucovorin 500mg/m2 IV over 2 hours

Days 1, 8, 15, 22, 29, and 36: Fluorouracil 500mg/m2 IV push 1 hour after start of leucovorin.

Repeat cycle every 8 weeks (6 weeks on- followed by 2 weeks off-treatment), concurrent with:

Day 1: Bevacizumab 5mg/kg IV.

Repeat cycle every 2 weeks.

Selpercatinib83,84

Days 1-28: Selpercatinib 120mg orally twice daily (patients <50kg).

Repeat cycle every 4 weeks.

OR

Days 1-28: Selpercatinib 160mg orally twice daily (patients ≥50kg).

Repeat cycle every 4 weeks.

Simplified Biweekly infusional Fluorouracil/Leucovorin29,30,32,h

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400 mg/m2 IV push, followed by:

Days 1–2: Fluorouracil 1,200mg/m2 IV continuous infusion daily (2,400mg/m2 IV over 46–48 hours).

Repeat cycle every 2 weeks.

Simplified Biweekly infusional Fluorouracil/Leucovorin + Bevacizumab6,29,30,32,82,b,h

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400 mg/m2 IV push, followed by:

Days 1–2: Fluorouracil 1,200mg/m2 IV continuous infusion daily (2,400mg/m2 IV over 46–48 hours)

Day 1: Bevacizumab 5mg/kg IV.

Repeat cycle every 2 weeks.

Trastuzumab + Lapatinib

(HER2-amplified and RAS and BRAF WT)85-87,q,r

Days 1-28: Lapatinib 1,000mg orally once daily.

Repeat cycle every 4 weeks, concurrent with:

Day 1 of Cycle 1: Trastuzumab 4mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 2mg/kg IV over 30 minutes.

Repeat cycle weekly.

Trastuzumab + Pertuzumab (HER2-amplified and RAS and BRAF WT)85,88,89,q,r

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes

Day 1 of Cycle 1: Pertuzumab 840mg IV over 60 minutes, followed by:

Day 1 beginning with Cycle 2: Petruzumab 420mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Trifluridine + Tipiracil90,91,p

Days 1–5 and 8–12: Trifluridine + Tipiracil 35mg/m2 up to a maximum dose of 80mg/dose (based on the trifluridine component) orally twice daily.

Repeat cycle every 4 weeks.

Trifluridine + Tipiracil + Bevacizumab6,90,92,b,p

Days 1–5 and 8–12: Trifluridine + Tipiracil 35mg/m2 up to a maximum dose of 80mg/dose (based on the trifluridine component) orally twice daily.

Days 1,15: Bevacizumab 5mg/kg IV.

Repeat cycle every 4 weeks.

Weekly Fluorouracil/ Leucovorin29,30,93,h

Day 1: Leucovorin 20mg/m2 IV over 2 hours

Day 1: Fluorouracil 500mg/m2 IV push 1 hour after the start of Leucovorin infusion.

Repeat cycle weekly.

OR

Day 1: Leucovorin 500mg/m2 IV over 2 hours

Day 1: Fluorouracil 2,600mg/m2 continuous infusion over 24 hours.

Repeat cycle weekly.

Weekly Fluorouracil/Leucovorin + Bevacizumab6,29,30,82,93,b,h

Day 1: Leucovorin 20mg/m2 IV over 2 hours

Day 1: Fluorouracil 500mg/m2 IV push administered one hour after start of Leucovorin infusion.

Repeat cycle weekly, concurrent with:

Day 1: Bevacizumab 5mg/kg IV.

Repeat every 2 weeks.

OR

Day 1: Leucovorin 500mg/m2 IV over 2 hours

Day 1: Fluorouracil 2,600mg/m2 IV continuous infusion over 24 hours.

Repeat cycle weekly, concurrent with:

Day 1: Bevacizumab 5mg/kg IV.

Repeat every 2 weeks.

▶Neoadjuvant/Adjuvant Therapy for Nonmetastatic Colon Cancer1,a

REGIMEN

DOSING

Capecitabine2-5

Days 1–14: Capecitabine 1,000–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks for 8 cycles (adjuvant).

OR

Days 1–14: Capecitabine 850–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks for 2-3 months (neoadjuvant).

CAPEOX2,6,9-12

Days 1–15: Capecitabine 1,000mg/m2 orally twice daily (beginning in the evening of Day 1 and ending the morning of Day 15)

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 3-8 cycles (adjuvant or neoadjuvant).

mFOLFOX69,29,30,59-62,c,h,k,l

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1,200mg/m2/day (total 2,400mg/m2 over46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks for 4-12 cycles (neoadjuvant or adjuvant).

Pembrolizumab

(MSI-H/dMMR tumors)74-76,f

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat every 3 weeks (neoadjuvant).

OR

Day 1: Pembrolizumab 2mg/kg IV over 30 minutes

Repeat cycle every 3 weeks (neoadjuvant).

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat every 6 weeks (neoadjuvant).

Nivolumab

(MSI-H/dMMR tumors)69,70,f

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat every 2 weeks (neoadjuvant).

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks (neoadjuvant).

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks (neoadjuvant).

Nivolumab/Ipilimumab

(MSI-H/dMMR tumors)69,71,72,f

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks (neoadjuvant).

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 3mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks (neoadjuvant)

OR

Day 1: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks (neoadjuvant).

Roswell Park regimen Fluorouracil/Leucovorin29,30,80,81,h

Days 1,8,15,22,29, and 36: Leucovorin 500mg/m2 IV over 2 hours

Days 1,8,15,22,29, and 36: Fluorouracil 500mg/m2 IV push 1 hour after start of Leucovorin.

Repeat cycle every 8 weeks (6 weeks on- followed by 2 weeks off-treatment) for 4 cycles (neoadjuvant or adjuvant).

Simplified Biweekly infusional Fluorouracil/Leucovorin29,30,32,h

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400 mg/m2 IV push, followed by:

Days 1–2: Fluorouracil 1,200mg/m2 IV continuous infusion daily (2,400mg/m2 IV over 46–48 hours).

Repeat cycle every 2 weeks for 12 cycles (neoadjuvant or adjuvant).

▶Chemoradiation Therapy for Locally Unresectable or Medically Inoperable Disease1,a

REGIMEN

DOSING

Capecitabine + RT2,94,95

Days 1-5: Capecitabine 825mg/m2 IV twice daily.

Repeat cycle for 5 weeks with concurrent RT.

Continuous Infusion Fluorouracil + RT29,94,h

Days 1-5 or 1-7: Fluorouracil 225mg/m2 IV continuous infusion over 24 hours.

Repeat cycle weekly for 5 weeks with concurrent RT.

Fluorouracil/Leucovorin + RT29,30,96,h

Days 1-4 and 29-32: Leucovorin 20mg/m2 IV push

Days 1-4 and 29-32: Fluorouracil 400mg/m2 IV push.

Administer for one 5-week cycle with concurrent RT (for patients not able to tolerate capecitabine or infusional Fluorouracil).

  a Abbreviations: dMMR, mismatch repair deficient; FOLFIRI, fluorouracil/leucovorin/irinotecan; FOLFOX, fluorouracil/leucovorin/oxaliplatin; FOLFOXIRI, fluorouracil/­leucovorin/oxaliplatin/irinotecan; MSI-H, microsatellite instability-high; RT, radiation therapy; WT, wild type.

  b A biosimilar may be substituted for Bevacizumab if clinically appropriate.

  c For metastatic indication, discontinuation of Oxaliplatin should be strongly considered after 3-4 months of therapy (or sooner if neuropathy grade 2 or greater develops) while maintaining other agents until time of progression. Oxaliplatin may be reintroduced if it was discontinued for neurotoxicity rather than for disease progression.

  d For Cetuximab: Predication for hypersensitivity and/or infusion reactions is required. The recommended dosing is:
   ⦁ Diphenhydramine 12.5-50mg IV30 minutes pre-Cetuximab.

  e Cetuximab and panitumumab should only be used for left-sided tumors. The panel defines the left side of the colon as splenic flexure to rectum.

  f Early- and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors. Patients with neurologic or life-threatening autoimmune disorders as well as receiving high levels of immunosuppression for their underlying disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing intensive monitoring and supportive care.

  g If no previous treatment with an immune checkpoint inhibitor.

  h Leucovorin 400mg/m2 IV is the equivalent of Levoleucovorin 200mg/m2.

  i Irinotecan should be used with caution in patients with Gilbert syndrome or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established.

  j For Ramucirumab: Premedication for infusion reactions is required. The recommended dosing is:
   ⦁ Diphenhydramine 12.5-50mg IV 30 minutes pre-Ramucirumab.

  k Leucovorin infusion time should match the infusion time of Oxaliplatin when these agents were given concurrently.

  l CSFs may be considered for primary prophylaxis based on the febrile neutropenia (FN) risk of the chemotherapy regimen.

  m FOLFIRINOX should be strongly considered in patients with excellent performance status.

  n FOLFIRINOX is recommended instead of FOLFOXIRI because FOLFOXIRI uses high dose of fluorouracil and have been shown to have greater toxicity with fluorouracil.

  o FOLFIRINOX; FOLFIRINOX +bev; FOLFIRINOX +cetux; FOLFIRINOX + pani: Myeloid growth factor therapy recommended.

  p Regorafenib or Trifluridine + Tipiracil with or without Bevacizumab are treatment options for patients who have progressed through all available regimens.

  q A biosimilar may be substituted for Trastuzumab if clinically appropriate.

  r If no prior treatment with HER2 inhibitor.

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(Revised 12/2022; NCCN Colon Cancer Guidelines v2.2022) © 2022 by Haymarket Media, Inc.

This article originally appeared on Cancer Therapy Advisor

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Gastrointestinal Cancer Treatment Regimens