Advanced/Metastatic CRC

-  mFOLFOX 6

Oxaliplatin 85 mg/m2 IV day 1z Leucovorin 400 mg/m2 IV day 1aa

5-FU 400 mg/m2 IV bolus on day 1, followed by 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46–48 hours) IV continuous infusion

Repeat every 2 weeks

-  mFOLFOX 7

Oxaliplatin 85 mg/m2 IV day 1z Leucovorin 400 mg/m2 IV day 1aa

5-FU 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46–48 hours) IV continuous infusion

Repeat every 2 weeks

-  FOLFOX + bevacizumab

 Bevacizumab  mg/kg IV, day 1 Repeat every 2 weeks

- FOLFOX + panitumumab  (KRAS/NRAS/BRAF WT)

Panitumumab 6 mg/kg IV over 60 minutes, day 1 ---Repeat every 2 weeks

-  FOLFOX + cetuximab (KRAS/NRAS/BRAF WT)

Cetuximab 400 mg/m2 IV over 2 hours first infusion, followed by 250 mg/m2 IV over 60 minutes weekly or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks (preferred for every 2 weeks)

-  CAPEOX8

Oxaliplatin 130 mg/m2 IV day 1z

Capecitabine 1000cc mg/m2 twice daily PO for 14 days

Repeat every 3 weeks

-  CAPEOX + bevacizumab

Oxaliplatin 130 mg/m2 IV day 1z

Capecitabine 1000cc mg/m2 PO twice daily for 14 days

Bevacizumab 7.5 mg/kg IV day 1 Repeat every 3 weeks

CAPEOX + cetuximab (KRAS/NRAS/BRAF WT)

Cetuximab 400 mg/m2 IV over 2 hours first infusion, followed by 250 mg/m2 IV over 60 minutes weekly or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks (preferred for every 2 weeks)

CAPEOX + panitumumab9-11 (KRAS/NRAS/BRAF WT)

Panitumumab 6 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks

FOLFIRI

Irinotecan 180 mg/m2 IV over 30–90 minutes, day 1

Leucovorinaa 400 mg/m2 IV infusion to match duration of irinotecan infusion,

day 1

5-FU 400 mg/m2 IV bolus day 1, followed by 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46–48 hours) continuous infusion

Repeat every 2 weeks

-  FOLFIRI + bevacizumab

Bevacizumab 5 mg/kg IV, day 1 Repeat every 2 weeks

-  FOLFIRI + cetuximab (KRAS/NRAS/BRAF WT)

Cetuximab 400 mg/m2 IV over 2 hours first infusion, followed by 250 mg/m2 IV over 60 minutes weekly or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks (preferred

for every 2 weeks)

-  FOLFIRI + panitumumab (KRAS/NRAS/BRAF WT)

Panitumumab 6 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks

- FOLFIRINOX20

Oxaliplatin 85 mg/m² IV on day 1,z leucovorin 400 mg/m² IV over 2 hours on day 1, irinotecan 165–180 mg/m² IV over 30–90 minutes on day 1, 5-FU 400 mg/m² IV push day 1, 5-FU 1200 mg/m²/day x 2 days (total 2400 mg/m² over 46 hours) continuous infusion.

Repeat every 2 weeks

-  Modified FOLFIRINOX

Oxaliplatin 85 mg/m² IV on day 1,z leucovorin 400 mg/m² IV over 2 hours on day 1, irinotecan 150 mg/m² IV over 30–90 minutes on day 1, 5-FU 1200 mg/m²/day x 2 days (total 2400 mg/m² over 46 hours) continuous infusion. Repeat every 2 weeks

-  FOLFIRINOX or mFOLFIRINOX + bevacizumab

Bevacizumab 5 mg/kg IV, day 1

Repeat every 2 weeks

-  IROX

Oxaliplatin 85 mg/m2 IV

followed by irinotecan 200 mg/m2 over 30–90 minutes every 3 weeks

-  IROX + bevacizumab

Bevacizumab 7.5 mg/kg IV on day 1 Repeat every 3 weeks

-  Bolus or infusional 5-FU/leucovorin Roswell Park regimen

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

5-FU 500 mg/m2 IV bolus 1 hour after start of leucovorin,

days 1, 8, 15, 22, 29, and 36

Repeat every 8 weeks

-  Simplified biweekly infusional 5-FU/leucovorin (sLV5FU2)

Leucovorinaa 400 mg/m2 IV over 2 hours on day 1,

followed by 5-FU bolus 400 mg/m2 followed by 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46–48 hours) continuous infusion Repeat every 2 weeks

Weekly Leucovorin 20 mg/m2 IV over 2 hours on day 1, 5-FU 500 mg/ m2 IV bolus injection 1 hour after the start of leucovorin. Repeat weekly27

or

5-FU 2600 mg/m2 by 24-hour infusion plus leucovorin 500 mg/m2 Repeat every week

-  Bolus or infusional 5-FU + bevacizumab

Bevacizumab 5 mg/kg IV on day 1

Repeat every 2 weeks

-  Capecitabine

Capecitabine 850–1250 mg/m2 PO twice daily for 14 days Repeat every 3 weeks

- Capecitabine + bevacizumab

Bevacizumab 7.5 mg/kg IV, day 1 Repeat every 3 weeks

l  Irinotecan

Irinotecan 125 mg/m2 IV over 30–90 minutes, days 1 and 8 Repeat every 3 weeks

or Irinotecan 180 mg/m2 IV over 30–90 minutes, day 1 Repeat every 2 weeks

or Irinotecan 300–350 mg/m2 IV over 30–90 minutes, day 1 Repeat every 3 weeks

-  Irinotecan + cetuximab (KRAS/NRAS/BRAF WT)

Cetuximab 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly32

or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks16

(preferred for every 2 weeks)

-  Irinotecan + panitumumab17,33 (KRAS/NRAS/BRAF WT)

Panitumumab 6 mg/kg IV over 60 minutes every 2 weeks

-  Irinotecan + bevacizumab34,bb Irinotecan 180 mg/m2 IV, day 1

Bevacizumab 5 mg/kg IV, day 1 Repeat every 2 weeks

or

Irinotecan 300–350 mg/m2 IV, day 1

Bevacizumab 7.5 mg/kg IV, day 1 Repeat every 3 weeks

Cetuximab (KRAS/NRAS/BRAF WT)

Cetuximab 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly32

or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks16

(preferred for every 2 weeks)

Panitumumab35 (KRAS/NRAS/BRAF WT)

Panitumumab 6 mg/kg IV over 60 minutes every 2 weeks

- Trastuzumab + pertuzumab

(HER2-amplified and RAS and BRAF WT)

Trastuzumab 8 mg/kg IV loading dose on day 1 of cycle 1, followed by 6 mg/kg IV every 21 days

Pertuzumab 840 mg IV loading dose on day 1 of cycle 1, followed by 420 mg IV every 21 days

-  Trastuzumab + lapatinib

(HER2-amplified and RAS and BRAF WT)

Trastuzumab 4 mg/kg IV loading dose on day 1 of cycle 1, followed by 2 mg/kg IV weekly

Lapatinib 1000 mg PO daily